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Journal articles on the topic 'Ligand interaction'
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van Heerden, Tracey, and Eric van Steen. "Metal–support interaction on cobalt based FT catalysts – a DFT study of model inverse catalysts." Faraday Discussions 197 (2017): 87–99. http://dx.doi.org/10.1039/c6fd00201c.
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It is challenging to isolate the effect of metal–support interactions on catalyst reaction performance. In order to overcome this problem, inverse catalysts can be prepared in the laboratory and characterized and tested at relevant conditions. Inverse catalysts are catalysts where the precursor to the catalytically active phase is bonded to a support-like ligand. We can then view the metal–support interaction as a ligand interaction with the support acting as a supra-molecular ligand. Importantly, laboratory studies have shown that these ligands are still present after reduction of the catalyst. By varying the quantity of these ligands present on the surface, insight into the positive effect SMSI have during a reaction is gained. Here, we present a theoretical study of mono-dentate alumina support based ligands, adsorbed on cobalt surfaces. We find that the presence of the ligand may significantly affect the morphology of a cobalt crystallite. With Fischer–Tropsch synthesis in mind, the CO dissociation is used as a probe reaction, with the ligand assisting the dissociation, making it feasible to dissociate CO on the dense fcc Co(111) surface. The nature of the interaction between the ligand and the probe molecule is characterized, showing that the support-like ligands’ metal centre is directly interacting with the probe molecule.
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Piosik, Jacek, Kacper Wasielewski, Anna Woziwodzka, Wojciech Śledź, and Anna Gwizdek-Wiśniewska. "De-intercalation of ethidium bromide and propidium iodine from DNA in the presence of caffeine." Open Life Sciences 5, no. 1 (February 1, 2010): 59–66. http://dx.doi.org/10.2478/s11535-009-0077-2.
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AbstractCaffeine (CAF) is capable of interacting directly with several genotoxic aromatic ligands by stacking aggregation. Formation of such hetero-complexes may diminish pharmacological activity of these ligands, which is often related to its direct interaction with DNA. To check these interactions we performed three independent series of spectroscopic titrations for each ligand (ethidium bromide, EB, and propidium iodine, PI) according to the following setup: DNA with ligand, ligand with CAF and DNA-ligand mixture with CAF. We analyzed DNA-ligand and ligand-CAF mixtures numerically using well known models: McGhee-von Hippel model for ligand-DNA interactions and thermodynamic-statistical model of mixed association of caffeine with aromatic ligands developed by Zdunek et al. (2000). Based on these models we calculated association constants and concentrations of mixture components using a novel method developed here. Results are in good agreement with parameters calculated in separate experiments and demonstrate de-intercalation of EB and PI molecules from DNA caused by CAF.
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Karasev, Dmitry, Boris Sobolev, Alexey Lagunin, Dmitry Filimonov, and Vladimir Poroikov. "Prediction of Protein–ligand Interaction Based on Sequence Similarity and Ligand Structural Features." International Journal of Molecular Sciences 21, no. 21 (October 31, 2020): 8152. http://dx.doi.org/10.3390/ijms21218152.
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Computationally predicting the interaction of proteins and ligands presents three main directions: the search of new target proteins for ligands, the search of new ligands for targets, and predicting the interaction of new proteins and new ligands. We proposed an approach providing the fuzzy classification of protein sequences based on the ligand structural features to analyze the latter most complicated case. We tested our approach on five protein groups, which represented promised targets for drug-like ligands and differed in functional peculiarities. The training sets were built with the original procedure overcoming the data ambiguity. Our study showed the effective prediction of new targets for ligands with an average accuracy of 0.96. The prediction of new ligands for targets displayed the average accuracy 0.95; accuracy estimates were close to our previous results, comparable in accuracy to those of other methods or exceeded them. Using the fuzzy coefficients reflecting the target-to-ligand specificity, we provided predicting interactions for new proteins and new ligands; the obtained accuracy values from 0.89 to 0.99 were acceptable for such a sophisticated task. The protein kinase family case demonstrated the ability to account for subtle features of proteins and ligands required for the specificity of protein–ligand interaction.
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Ferreira de Freitas, Renato, and Matthieu Schapira. "A systematic analysis of atomic protein–ligand interactions in the PDB." MedChemComm 8, no. 10 (2017): 1970–81. http://dx.doi.org/10.1039/c7md00381a.
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We compiled a list of 11 016 unique structures of small-molecule ligands bound to proteins representing 750 873 protein–ligand atomic interactions, and analyzed the frequency, geometry and the impact of each interaction type. The most frequent ligand–protein atom pairs can be clustered into seven interaction types.
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Marsh, Lorraine. "Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites." BioMed Research International 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/746980.
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Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorableΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorableΔGbecause of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total bindingΔGarising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where “nonspecific” interactions contribute to biological function.
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Kato, Koya, and George Chikenji. "1P266 Development of Ligand Based Virtual Screening considering protein-ligand interaction(22A. Bioinformatics: Structural genomics,Poster)." Seibutsu Butsuri 53, supplement1-2 (2013): S150. http://dx.doi.org/10.2142/biophys.53.s150_1.
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KROGSDAM, Anne-M., Curt A. F. NIELSEN, Søren NEVE, Dorte HOLST, Torben HELLEDIE, Bo THOMSEN, Christian BENDIXEN, Susanne MANDRUP, and Karsten KRISTIANSEN. "Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor δ-mediated transactivation." Biochemical Journal 363, no. 1 (March 22, 2002): 157–65. http://dx.doi.org/10.1042/bj3630157.
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The nuclear receptor corepressor (NCoR) was isolated as a peroxisome-proliferator-activated receptor (PPAR) δ interacting protein using the yeast two-hybrid system. NCoR interacted strongly with the ligand-binding domain of PPARδ, whereas interactions with the ligand-binding domains of PPARγ and PPARα were significantly weaker. PPAR—NCoR interactions were antagonized by ligands in the two-hybrid system, but were ligand-insensitive in in vitro pull-down assays. Interaction between PPARδ and NCoR was unaffected by coexpression of retinoid X receptor (RXR) α. The PPARδ—RXRα heterodimer bound to an acyl-CoA oxidase (ACO)-type peroxisome-proliferator response element recruited a glutathione S-transferase—NCoR fusion protein in a ligand-independent manner. Contrasting with most other nuclear receptors, PPARδ was found to interact equally well with interaction domains I and II of NCoR. In transient transfection experiments, NCoR and the related silencing mediator for retinoid and thyroid hormone receptor (SMRT) were shown to exert a marked dose-dependent repression of ligand-induced PPARδ-mediated transactivation; in addition, transactivation induced by the cAMP-elevating agent forskolin was efficiently reduced to basal levels by NCoR as well as SMRT coexpression. Our results suggest that the transactivation potential of liganded PPARδ can be fine-tuned by interaction with NCoR and SMRT in a manner determined by the expression levels of corepressors and coactivators.
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Beshnova, Daria A., Joana Pereira, and Victor S. Lamzin. "Estimation of the protein–ligand interaction energy for model building and validation." Acta Crystallographica Section D Structural Biology 73, no. 3 (March 1, 2017): 195–202. http://dx.doi.org/10.1107/s2059798317003400.
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Macromolecular X-ray crystallography is one of the main experimental techniques to visualize protein–ligand interactions. The high complexity of the ligand universe, however, has delayed the development of efficient methods for the automated identification, fitting and validation of ligands in their electron-density clusters. The identification and fitting are primarily based on the density itself and do not take into account the protein environment, which is a step that is only taken during the validation of the proposed binding mode. Here, a new approach, based on the estimation of the major energetic terms of protein–ligand interaction, is introduced for the automated identification of crystallographic ligands in the indicated binding site withARP/wARP. The applicability of the method to the validation of protein–ligand models from the Protein Data Bank is demonstrated by the detection of models that are `questionable' and the pinpointing of unfavourable interatomic contacts.
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Folkertsma, Simon, Paula I. van Noort, Arnold de Heer, Peter Carati, Ralph Brandt, Arie Visser, Gerrit Vriend, and Jacob de Vlieg. "The Use of in Vitro Peptide Binding Profiles and in Silico Ligand-Receptor Interaction Profiles to Describe Ligand-Induced Conformations of the Retinoid X Receptor α Ligand-Binding Domain." Molecular Endocrinology 21, no. 1 (January 1, 2007): 30–48. http://dx.doi.org/10.1210/me.2006-0072.
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Abstract It is hypothesized that different ligand-induced conformational changes can explain the different interactions of nuclear receptors with regulatory proteins, resulting in specific biological activities. Understanding the mechanism of how ligands regulate cofactor interaction facilitates drug design. To investigate these ligand-induced conformational changes at the surface of proteins, we performed a time-resolved fluorescence resonance energy transfer assay with 52 different cofactor peptides measuring the ligand-induced cofactor recruitment to the retinoid X receptor-α (RXRα) in the presence of 11 compounds. Simultaneously we analyzed the binding modes of these compounds by molecular docking. An automated method converted the complex three-dimensional data of ligand-protein interactions into two-dimensional fingerprints, the so-called ligand-receptor interaction profiles. For a subset of compounds the conformational changes at the surface, as measured by peptide recruitment, correlate well with the calculated binding modes, suggesting that clustering of ligand-receptor interaction profiles is a very useful tool to discriminate compounds that may induce different conformations and possibly different effects in a cellular environment. In addition, we successfully combined ligand-receptor interaction profiles and peptide recruitment data to reveal structural elements that are possibly involved in the ligand-induced conformations. Interestingly, we could predict a possible binding mode of LG100754, a homodimer antagonist that showed no effect on peptide recruitment. Finally, the extensive analysis of the peptide recruitment profiles provided novel insight in the potential cellular effect of the compound; for the first time, we showed that in addition to the induction of coactivator peptide binding, all well-known RXRα agonists also induce binding of corepressor peptides to RXRα.
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Rifai, Yusnita. "SEARCH FOR GLIOMA DIRECT BINDING SITE OF ALKALOID USING PROTEIN-LIGAND ANT SYSTEM®." Asian Journal of Pharmaceutical and Clinical Research 11, no. 15 (October 3, 2018): 65. http://dx.doi.org/10.22159/ajpcr.2018.v11s3.30034.
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Objective: This research aims to know the best affinity and the best chemical conformation of anticancer compounds from alkaloid groups that have closed direction to Glioma-associated oncogene using protein-ligand ant system (PLANTS®). The interaction energy and hydrogen bond are included as evaluated targets.Methods: In this research, 27 ligands with root mean square deviation score at 1.614 Å and cyclopamine as native ligand are used. Meanwhile, staurosporinone acts as gliomas directed-binding-site-internal-control. Each ligand is docked in GLI with Protein Data Bank code 2GLI using two methods, GLI contains water and without water.Results: PLANTS® score for native ligand in the first and the second method is −73.9002 and −73.2700, respectively. Pancracristine, homoharringtonine, and sanguinarine showed PLANTS® score closed to the cyclopamine score result, but their hydrogen bond interaction differed from native ligan interaction. Evodiamine ligand has a good score and hydrogen bond to the same amino acid of protein GLI, which are GLU 175 and THR 173. This result indicated that evodiamine has the same identical mechanism as staurosporinone.Conclusion: The evodiamine is determined to have the same working mechanism as a GLI inhibitor.
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Baskaran, Karthika Perampattu, Arunagiri Arumugam, Ruckmani Kandasamy, and Shanmugarathinam Alagarsamy. "INSILICO METHOD FOR PREDICTION OF MAXIMUM BINDING AFFINITY AND LIGAND – PROTEIN INTERACTION STUDIES ON ALZHEIMER’S DISEASE." International Journal of Research -GRANTHAALAYAH 8, no. 11 (December 19, 2020): 362–70. http://dx.doi.org/10.29121/granthaalayah.v8.i11.2020.2472.
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The aim of this study is to perform the molecular docking, identifying the drug likeness, ADME properties of drugs, Ligand-Protein interactions using different softwares. Due to the excess activity of Acetylcholinesterase, plaque formation and tau protein aggregation in the brain is the main cause for the Alzheimer’s disease. The interaction of Donepezil, Rivastigmine and Chlorzoxazone against AChE protein crystal structure (4EY5, 4EY6, 4EY7) using molecular docking were analyzed. Docking results of Rivastigmine and Chlorzoxazone were compared with Donepezil (widely used drug for Alzheimer’s disease) to identify the binding affinity. To verify whether Chlorzoxazone could act similarly as effective drug of Donepezil and also finding in which protein structure, ligands could bind effectively were employed using BIOVIA Discovery Studio software. Among those ligands interaction with all protein structure, 4EY7 on Rivastigmine (-7.1 kcal/mol) exhibits maximum binding affinity. The interactions of three ligands were compared with one another, in that Hydrogen bond formation of Chlorzoxazone and Donepezil with 4EY6 and 4EY7 interacting the similar aminoacids residues (4EY6-ARG165; 4EY7-ASP74) were studied using insilico studies .
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Aziz, Fitri Kusvila, Cantika Nukitasari, Fauziyah Ardli Oktavianingrum, Lita Windy Aryati, and Broto Santoso. "Hasil In Silico Senyawa Z12501572, Z00321025, SCB5631028 dan SCB13970547 dibandingkan Turunan Zerumbon terhadap Human Liver Glycogen Phosphorylase (1l5Q) sebagai Antidiabetes." Jurnal Kimia VALENSI 2, no. 2 (November 30, 2016): 120–24. http://dx.doi.org/10.15408/jkv.v2i2.4170.
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Abstrak Human Liver Glycogen Phosphorylase (HLGP), suatu katalis glikogen yang mengontrol pelepasan glukosa-1-fosfat glikogen dari hati. Enzim ini mempunyai peran sentral dalam luaran glukosa hati sehingga menjadi target obat antidiabetik. Kajian docking dilakukan pada komputer dengan prosesor Intel Pentium, RAM 1 GB dan Windows 7. Ligan yang digunakan adalah senyawa obat (Z12501572, Z00321025, SCB5631028 dan SCB13970547), dataset pembanding aktif glycogen phosphorylase outer dimer site (PYGL-out) dan decoysdari www.dekois.com dan turunan zerumbon. Protein dipisahkan dari ligan nativ dan semua ligan beserta protein dikonversi menggunakan PyRx. Visualisasi interaksi ligan-protein dihasilkan dengan program Protein-Ligand Interaction Profiler (PLIP) dan PyMOL. Senyawa ZER11 memiliki binding energy terbaik, yaitu -7.11 kkal/mol (untuk metode LGA dan GA) dan -4.08 kkal/mol untuk metode SA. Nilai binding energy tersebut lebih rendah dari pada nilai untuk ligan native dan satu dari keempat senyawa obat, terlebih jika dibandingkan dengan bindingaffinity dari dataset dan decoys. Interaksi ligan-protein pada ketiga metode tersebut ditemukan sangat bervariasi. Hal berbeda terjadi untuk metode Vina, bindingenergy ZER11 (-9.9 kkal/mol) lebih baik dibandingkan dengan ligan native dan keempat senyawa obat. Senyawa ZER11 memiliki residu interaksi yang sama dengan ligan native pada TRP67 dan LYS191 untuk metode Vina. Kata kunci: PDBID-1L5Q, AutoDock, docking molekuler, vina, antidiabetes Abstract Human Liver Glycogen Phosphorylase (HLGP) can catalyze glycogen and control the release of glucose-1-phosphate of glycogen from the liver. This enzyme has a central role in output rule of liver glucose as it can be used as an antidiabetic drug targets. Docking studies were carried out on PC with Intel Pentium, 1 GB RAM, in environment of Windows 7. Ligands used are drug compounds (Z12501572, Z00321025, SCB5631028 and SCB13970547), the active dataset comparator wasglycogenphosphorylase outer dimer site (PYGL-out) and decoys from www.dekois.com andzerumbonederivates. Protein was separated from its native ligand and all ligands including the protein were converted to pdbqt using PyRx. The interaction of protein-ligand was visualized using software of PLIP and PyMOL. Compound of ZER11 had the best binding energy were -7.11 kcal/mol (LGA and GA) and -4.08 kcal/mol (SA). The binding energy value was lower than the ligand native and one of the four drug compounds, especially compared with the binding affinity of dataset and decoys. Vice versa, for Vina method, the value of ligand binding protein for ZER11 (-9.9 kcal/mol) was better than the ligand native and all of the fourth drugcompounds. Vina result showed that ZER11 had the same residual interaction as the ligand native, which are TRP67 and LYS191. Keyword: PDBID-1L5Q, AutoDock, molecular docking, vina, antidiabetic DOI: http://dx.doi.org/10.15408/jkv.v0i0.4170
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Langelaan, David N., and Jan K. Rainey. "Membrane catalysis of peptide–receptor bindingThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process." Biochemistry and Cell Biology 88, no. 2 (April 2010): 203–10. http://dx.doi.org/10.1139/o09-129.
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The membrane catalysis hypothesis states that a peptide ligand activates its target receptor after an initial interaction with the surrounding membrane. Upon membrane binding and interaction, the ligand is structured such that receptor binding and activation is encouraged. As evidence for this hypothesis, there are numerous studies concerning the conformation that peptides adopt in membrane mimetic environments. This mini-review analyzes the features of ligand peptides with an available high-resolution membrane-induced structure and a characterized membrane-binding region. At the peptide–membrane interface, both amphipathic helices and turn structures are commonly formed in peptide ligands and both hydrophobic and electrostatic interactions can be responsible for membrane binding. Apelin is the ligand to the G-protein coupled receptor (GPCR) named APJ, with various important physiological effects, which we have recently characterized both in solution and bound to anionic micelles. The structural changes that apelin undergoes when binding to micelles provide strong evidence for membrane catalysis of apelin–APJ interactions.
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Colvin, Richard A., Gabriele S. V. Campanella, Lindsay A. Manice, and Andrew D. Luster. "CXCR3 Requires Tyrosine Sulfation for Ligand Binding and a Second Extracellular Loop Arginine Residue for Ligand-Induced Chemotaxis." Molecular and Cellular Biology 26, no. 15 (August 1, 2006): 5838–49. http://dx.doi.org/10.1128/mcb.00556-06.
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ABSTRACT CXCR3 is a G-protein-coupled seven-transmembrane domain chemokine receptor that plays an important role in effector T-cell and NK cell trafficking. Three gamma interferon-inducible chemokines activate CXCR3: CXCL9 (Mig), CXCL10 (IP-10), and CXCL11 (I-TAC). Here, we identify extracellular domains of CXCR3 that are required for ligand binding and activation. We found that CXCR3 is sulfated on its N terminus and that sulfation is required for binding and activation by all three ligands. We also found that the proximal 16 amino acid residues of the N terminus are required for CXCL10 and CXCL11 binding and activation but not CXCL9 activation. In addition, we found that residue R216 in the second extracellular loop is required for CXCR3-mediated chemotaxis and calcium mobilization but is not required for ligand binding or ligand-induced CXCR3 internalization. Finally, charged residues in the extracellular loops contribute to the receptor-ligand interaction. These findings demonstrate that chemokine activation of CXCR3 involves both high-affinity ligand-binding interactions with negatively charged residues in the extracellular domains of CXCR3 and a lower-affinity receptor-activating interaction in the second extracellular loop. This lower-affinity interaction is necessary to induce chemotaxis but not ligand-induced CXCR3 internalization, further suggesting that different domains of CXCR3 mediate distinct functions.
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Mondoro, TH, CD Wall, MM White, and LK Jennings. "Selective induction of a glycoprotein IIIa ligand-induced binding site by fibrinogen and von Willebrand factor." Blood 88, no. 10 (November 15, 1996): 3824–30. http://dx.doi.org/10.1182/blood.v88.10.3824.bloodjournal88103824.
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Ligand-induced binding sites (LIBS) are neoantigenic regions of glycoprotein (GP)IIb-IIIa that are exposed upon interaction of the receptor with the ligand fibrinogen or the ligand recognition sequence (RGDS). LIBS have been suggested to contribute to postreceptor occupancy events such as full-scale platelet aggregation, adhesion to collagen, and clot retraction. This study examined the induction requirements of a GPIIIa LIBS with regard to ligand specificity. Through the use of the anti-LIBS D3, we report that this complex- activating antibody induces fibrinogen-and von Willebrand factor-binding to GPIIb-IIIa on intact platelets. Bound ligand was detected by flow cytometric analysis and platelet aggregation assays. These bound ligands increased the number of D3-binding sites and altered the affinity of D3 for GPIIb-IIIa on platelets. In contrast, activation of platelet GPIIb-IIIa by D3 did not increase the binding of another RGD- containing ligand, vitronectin. Furthermore, bound vitronectin on thrombin-stimulated platelets did not cause the expression of the D3 LIBS epitope. We conclude direct activation of GPIIb-IIIa in the absence of platelet activation results in selective ligand interaction and that D3 LIBS induction requires the binding of the multivalent ligands, fibrinogen or von Willebrand factor. Thus, the region of GPIIIa recognized by D3 may be an important regulatory domain in ligand- receptor interactions that directly mediate platelet aggregation.
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Sharma, Ankur, Annapoorni Rangarajan, and Rajan R. Dighe. "Antibodies against the extracellular domain of human Notch1 receptor reveal the critical role of epidermal-growth-factor-like repeats 25–26in ligand binding and receptor activation." Biochemical Journal 449, no. 2 (December 14, 2012): 519–30. http://dx.doi.org/10.1042/bj20121153.
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The Notch signalling pathway is implicated in a wide variety of cellular processes throughout metazoan development. Although the downstream mechanism of Notch signalling has been extensively studied, the details of its ligand-mediated receptor activation are not clearly understood. Although the role of Notch ELRs [EGF (epidermal growth factor)-like-repeats] 11–12 in ligand binding is known, recent studies have suggested interactions within different ELRs of the Notch receptor whose significance remains to be understood. Here, we report critical inter-domain interactions between human Notch1 ELRs 21–30 and the ELRs 11–15 that are modulated by calcium. Surface plasmon resonance analysis revealed that the interaction between ELRs 21–30 and ELRs 11–15 is ~10-fold stronger than that between ELRs 11–15 and the ligands. Although there was no interaction between Notch1 ELRs 21–30 and the ligands in vitro, addition of pre-clustered Jagged1Fc resulted in the dissociation of the preformed complex between ELRs 21–30 and 11–15, suggesting that inter-domain interactions compete for ligand binding. Furthermore, the antibodies against ELRs 21–30 inhibited ligand binding to the full-length Notch1 and subsequent receptor activation, with the antibodies against ELRs 25–26 being the most effective. These results suggest that the ELRs 25–26 represent a cryptic ligand-binding site which becomes exposed only upon the presence of the ligand. Thus, using specific antibodies against various domains of the Notch1 receptor, we demonstrate that, although ELRs 11–12 are the principal ligand-binding site, the ELRs 25–26 serve as a secondary binding site and play an important role in receptor activation.
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Lecut, Christelle, Véronique Arocas, Hans Ulrichts, Anthony Elbaz, Jean-Luc Villeval, Jean-Jacques Lacapère, Hans Deckmyn, and Martine Jandrot-Perrus. "Identification of Residues within Human Glycoprotein VI Involved in the Binding to Collagen." Journal of Biological Chemistry 279, no. 50 (October 4, 2004): 52293–99. http://dx.doi.org/10.1074/jbc.m406342200.
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Glycoprotein VI (GPVI) has a crucial role in platelet responses to collagen. Still, little is known about its interaction with its ligands. In binding assays using soluble or cell-expressed human GPVI, we observed that (i) collagen, and the GPVI-specific ligands collagen-related peptides (CRP) and convulxin, competed with one another for the binding to GPVI and (ii) monoclonal antibodies directed against the extracellular part of the human receptor displayed selective inhibitory properties on GPVI interaction with its ligands. Monoclonal antibody 9E18 strongly reduced the binding of GPVI to collagen/CRP, 3F8 inhibited its interaction with convulxin, whereas 9O12 prevented all three interactions. These observations suggest that ligand-binding sites are distinct, exhibiting specific features but at the same time also sharing some common residues participating in the recognition of these ligands. The epitope of 9O12 was mapped by phage display, along with molecular modeling of human GPVI, which allowed the identification of residues within GPVI potentially involved in ligand recognition. Site-directed mutagenesis revealed that valine 34 and leucine 36 are critical for GPVI interaction with collagen and CRP. The loop might thus be part of a collagen/CRP-binding site.
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Kostic, Ivana, Tatjana Andjelkovic, Darko Andjelkovic, Ruzica Nikolic, Aleksandar Bojic, Tatjana Cvetkovic, and Goran Nikolic. "Interaction of cobalt(II), nickel(II) and zinc(II) with humic-like ligands studied by ESI-MS and ion-exchange method." Journal of the Serbian Chemical Society 81, no. 3 (2016): 255–70. http://dx.doi.org/10.2298/jsc150917094k.
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An interaction of Co(II), Ni(II) and Zn(II) with humic acid and O-donor humic-like ligands was studied by ion-exchange and electrospray ionization - mass spectrometry (ESI-MS) method. Interactions were confirmed by differences between values of chromatogram peak areas for monocomponent (ligand) and binary systems (ligand with metal ion) by newly developed ESI-MS 5 ?L Loop injection technique. Schubert?s ion exchange method was used for determination of stability constants of formed complexes at pH 4.0 and I = 0.01. Comparing the values of log Kmn for complexes formed by dipositive metal ions with humic, benzoic and salicylic acids, it can be concluded that the interaction strengths of transitional series metals follow the Irving-Williams order: Co(II) < Ni(II) < Cu(II) > Zn(II). The obtained values of log Kmn indicate that Pb(II) ions effect the strongest interactions with all investigated ligands. Complexation of humic acids macromolecules possessing O-donor binding sites as major binding sites can be predicted and modelled following the same order of interaction strength like Irving-Williams order.
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Ozers, Mary Szatkowski, Kerry M. Ervin, Corrine L. Steffen, Jennifer A. Fronczak, Connie S. Lebakken, Kimberly A. Carnahan, Robert G. Lowery, and Thomas J. Burke. "Analysis of Ligand-Dependent Recruitment of Coactivator Peptides to Estrogen Receptor Using Fluorescence Polarization." Molecular Endocrinology 19, no. 1 (January 1, 2005): 25–34. http://dx.doi.org/10.1210/me.2004-0256.
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Abstract Ligand-dependent recruitment of coactivators to estrogen receptor (ER) plays an important role in transcriptional activation of target genes. Agonist-bound ER has been shown to adopt a favorable conformation for interaction with the LXXLL motifs of the coactivator proteins. To further examine the affinity and ligand dependence of the ER-coactivator interaction, several fluorescently tagged short peptides bearing an LXXLL motif (LXXLL peptide) from either natural coactivator sequences or random phage display sequences were used with purified ERα or ERβ in an in vitro high-throughput fluorescence polarization assay. In the presence of saturating amounts of ligand, several LXXLL peptides bound to ERα and ERβ with affinity ranging from 20–500 nm. The random phage display LXXLL peptides exhibited a higher affinity for ER than the natural single-LXXLL coactivator sequences tested. These studies indicated that ER agonists, such as 17β-estradiol or estrone, promoted the interaction of ER with the coactivator peptides, whereas antagonists such as 4-hydroxytamoxifen or ICI-182,780 did not. Different LXXLL peptides demonstrated different affinities for ER depending on which ligand was bound to the receptor, suggesting that the peptides were recognizing different receptor conformations. Using the information obtained from direct measurement of the affinity of the ER-LXXLL peptide interaction, the dose dependency (EC50) of various ligands to either promote or disrupt this interaction was also determined. Interaction of ER with the LXXLL peptide was observed with ligands such as 17β-estradiol, estriol, estrone, and genistein but not with ICI-182,780, 4-hydroxytamoxifen, clomiphene, or tamoxifen, resulting in distinct EC50 values for each ligand and correlating well with the ligand biological function as an agonist or antagonist. Ligand-dependent recruitment of the LXXLL peptide to ERβ was observed in the presence of the ERβ-selective agonist diarylpropionitrile, but not the ERα-selective ligand propyl pyrazole triol. This assay could be used to classify unknown ligands as agonists, antagonists, or partial modulators, based on either the receptor-coactivator peptide affinities or the dose dependency of this interaction in comparison with known compounds.
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Koehbach, Johannes, Thomas Stockner, Christian Bergmayr, Markus Muttenthaler, and Christian W. Gruber. "Insights into the molecular evolution of oxytocin receptor ligand binding." Biochemical Society Transactions 41, no. 1 (January 29, 2013): 197–204. http://dx.doi.org/10.1042/bst20120256.
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The design and development of selective ligands for the human OT (oxytocin) and AVP (arginine vasopressin) receptors is a big challenge since the different receptor subtypes and their native peptide ligands display great similarity. Detailed understanding of the mechanism of OT's interaction with its receptor is important and may assist in the ligand- or structure-based design of selective and potent ligands. In the present article, we compared 69 OT- and OT-like receptor sequences with regards to their molecular evolution and diversity, utilized an in silico approach to map the common ligand interaction sites of recently published G-protein-coupled receptor structures to a model of the human OTR (OT receptor) and compared these interacting residues within a selection of different OTR sequences. Our analysis suggests the existence of a binding site for OT peptides within the common transmembrane core region of the receptor, but it appears extremely difficult to identify receptor or ligand residues that could explain the selectivity of OT to its receptors. We remain confident that the presented evolutionary overview and modelling approach will aid interpretation of forthcoming OTR crystal structures.
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Peñaherrera, Ana. "Mechanical matching between a ligand and receptor." Faraday Discussions 184 (2015): 71–84. http://dx.doi.org/10.1039/c5fd00106d.
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Interactions between ligands and receptors and subsequent “locking” must involve some resistance to unbinding, manifesting itself as an interaction force. At body temperature, spontaneous unbinding will occur, however, external forces are required to accelerate this process. Bearing in mind the potential forces that the receptor–ligand complex is likely to be subjected to in a biological environment, it might be hypothesised that there is some mechanical matching between the receptor and ligand. To test this hypothesis, various receptor and ligand pairs were unfolded in their entirety in order to determine their total unfolding force. In this way, the total force to unfold the protein could be determined, allowing a comparison between ligand and receptor pairs. The interest of this work is to examine the interaction between five proteins and a mica surface by AFM without any modification to preserve the natural elastic properties of the protein molecules during the force measurements. The results showed a mechanical matching between GP120 (ligand) and CD4 (receptor) when analysing the total force required to unfold the same number of domains or events shown by the force distance curves of these proteins.
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Anand, Praveen, Deepesh Nagarajan, Sumanta Mukherjee, and Nagasuma Chandra. "ABS–Scan: In silico alanine scanning mutagenesis for binding site residues in protein–ligand complex." F1000Research 3 (September 9, 2014): 214. http://dx.doi.org/10.12688/f1000research.5165.1.
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Most physiological processes in living systems are fundamentally regulated by protein–ligand interactions. Understanding the process of ligand recognition by proteins is a vital activity in molecular biology and biochemistry. It is well known that the residues present at the binding site of the protein form pockets that provide a conducive environment for recognition of specific ligands. In many cases, the boundaries of these sites are not well defined. Here, we provide a web-server to systematically evaluate important residues in the binding site of the protein that contribute towards the ligand recognition through in silico alanine-scanning mutagenesis experiments. Each of the residues present at the binding site is computationally mutated to alanine. The ligand interaction energy is computed for each mutant and the corresponding ΔΔG values are computed by comparing it to the wild type protein, thus evaluating individual residue contributions towards ligand interaction. The server will thus provide clues to researchers about residues to obtain loss-of-function mutations and to understand drug resistant mutations. This web-tool can be freely accessed through the following address: http://proline.biochem.iisc.ernet.in/abscan/.
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Anand, Praveen, Deepesh Nagarajan, Sumanta Mukherjee, and Nagasuma Chandra. "ABS–Scan: In silico alanine scanning mutagenesis for binding site residues in protein–ligand complex." F1000Research 3 (December 1, 2014): 214. http://dx.doi.org/10.12688/f1000research.5165.2.
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Most physiological processes in living systems are fundamentally regulated by protein–ligand interactions. Understanding the process of ligand recognition by proteins is a vital activity in molecular biology and biochemistry. It is well known that the residues present at the binding site of the protein form pockets that provide a conducive environment for recognition of specific ligands. In many cases, the boundaries of these sites are not well defined. Here, we provide a web-server to systematically evaluate important residues in the binding site of the protein that contribute towards the ligand recognition through in silico alanine-scanning mutagenesis experiments. Each of the residues present at the binding site is computationally mutated to alanine. The ligand interaction energy is computed for each mutant and the corresponding ΔΔG values are calculated by comparing it to the wild type protein, thus evaluating individual residue contributions towards ligand interaction. The server will thus provide a ranked list of residues to the user in order to obtain loss-of-function mutations. This web-tool can be freely accessed through the following address: http://proline.biochem.iisc.ernet.in/abscan/.
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Chilmonczyk, Zdzisław. "Ligand-5-HT1A receptor interaction." Il Farmaco 55, no. 3 (March 2000): 191–93. http://dx.doi.org/10.1016/s0014-827x(00)00019-7.
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Reddy, A. Srinivas, H. S. Durga Amarnath, Raju S. Bapi, G. Madhavi Sastry, and G. Narahari Sastry. "Protein ligand interaction database (PLID)." Computational Biology and Chemistry 32, no. 5 (October 2008): 387–90. http://dx.doi.org/10.1016/j.compbiolchem.2008.03.017.
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Kobren, Shilpa Nadimpalli, and Mona Singh. "Systematic domain-based aggregation of protein structures highlights DNA-, RNA- and other ligand-binding positions." Nucleic Acids Research 47, no. 2 (December 7, 2018): 582–93. http://dx.doi.org/10.1093/nar/gky1224.
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Abstract Domains are fundamental subunits of proteins, and while they play major roles in facilitating protein–DNA, protein–RNA and other protein–ligand interactions, a systematic assessment of their various interaction modes is still lacking. A comprehensive resource identifying positions within domains that tend to interact with nucleic acids, small molecules and other ligands would expand our knowledge of domain functionality as well as aid in detecting ligand-binding sites within structurally uncharacterized proteins. Here, we introduce an approach to identify per-domain-position interaction ‘frequencies’ by aggregating protein co-complex structures by domain and ascertaining how often residues mapping to each domain position interact with ligands. We perform this domain-based analysis on ∼91000 co-complex structures, and infer positions involved in binding DNA, RNA, peptides, ions or small molecules across 4128 domains, which we refer to collectively as the InteracDome. Cross-validation testing reveals that ligand-binding positions for 2152 domains are highly consistent and can be used to identify residues facilitating interactions in ∼63–69% of human genes. Our resource of domain-inferred ligand-binding sites should be a great aid in understanding disease etiology: whereas these sites are enriched in Mendelian-associated and cancer somatic mutations, they are depleted in polymorphisms observed across healthy populations. The InteracDome is available at http://interacdome.princeton.edu.
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Hansson, E. M., F. Lanner, D. Das, A. Mutvei, U. Marklund, J. Ericson, F. Farnebo, et al. "Control of Notch-ligand endocytosis by ligand-receptor interaction." Journal of Cell Science 123, no. 17 (August 18, 2010): 2931–42. http://dx.doi.org/10.1242/jcs.073239.
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Hansson, E. M., F. Lanner, D. Das, A. Mutvei, U. Marklund, J. Ericson, F. Farnebo, et al. "Control of Notch-ligand endocytosis by ligand-receptor interaction." Development 137, no. 18 (August 24, 2010): e1-e1. http://dx.doi.org/10.1242/dev.057869.
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Sasaki, Yoichi, and Masaaki Abe. "Ligand-ligand redox interaction through some metal-cluster units." Chemical Record 4, no. 5 (2004): 279–90. http://dx.doi.org/10.1002/tcr.20021.
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Li, Huiqing, Jing Wei, Youming Dong, and Zhiyue Yu. "Interaction between 2-(p-toluidino)-6-naphthalenesulfonic acid sodium salt (TNS) and β-lactoglobulin." Canadian Journal of Chemistry 94, no. 8 (August 2016): 680–86. http://dx.doi.org/10.1139/cjc-2015-0450.
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The major bovine milk protein β-lactoglobulin (β-LG), a member of the lipocalin superfamily, can bind a wide range of ligands and act as a transporter. In the present study, the combination of the hydrophobic molecule 2-(p-toluidino)-6-naphthalenesulfonic acid sodium salt (TNS) with β-LG was analyzed using fluorescence spectroscopy and AutoDock modeling to discern the major binding sites of the protein and to determine the capacity of other small ligands to bind with β-LG by utilizing TNS as a reference. The experimental data indicate that in a neutral pH environment, TNS is located in the hydrophobic domain of the protein, 2.5 nm away from the Trp19 residues of β-LG. The binding constant of the small molecule to β-LG is (3.30 ± 0.32) × 106 (mol L–1)−1. An interaction model between the ligand and β-LG was developed, and AutoDock modeling also demonstrates that the ligand is located in the central hydrophobic calyx of β-LG within the regions covered by the Förster radius of the Trp19–ligand pair. Although the interaction between the ligand and β-LG is affected by increasing ion strength, pH change, and heat treatment, the complex is maintained until the secondary structure of β-LG is destroyed. Additionally, the ligand binding stabilizes the folding of β-LG. The binding constants of sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) to β-LG were obtained using competitive ligand binding measurements. With a sensitive fluorescence signal and stable complex, the ligand could be utilized as a reference to detect the binding of other small ligands to β-LG.
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Kuznetsov, Aleksei, and Jaak Järv. "Ligand structure controlled allostery in cAMP-dependent protein kinase catalytic subunit." Open Life Sciences 4, no. 2 (June 1, 2009): 131–41. http://dx.doi.org/10.2478/s11535-009-0012-6.
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AbstractProtein kinase A (cAMP dependent protein kinase catalytic subunit, EC 2.7.11.11) binds simultaneously ATP and a phosphorylatable peptide. These structurally dissimilar allosteric ligands influence the binding effectiveness of each other. The same situation is observed with substrate congeners, which reversibly inhibit the enzyme. In this review these allosteric effects are quantified using the interaction factor, which compares binding effectiveness of ligands with the free enzyme and the pre-loaded enzyme complex containing another ligand. This analysis revealed that the allosteric effect depends upon structure of the interacting ligands, and the principle “better binding: stronger allostery” observed can be formalized in terms of linear free-energy relationships, which point to similar mechanism of the allosteric interaction between the enzyme-bound substrates and/or inhibitor molecules. On the other hand, the type of effect is governed by ligand binding effectiveness and can be inverted from positive allostery to negative allostery if we move from effectively binding ligands to badly binding compounds. Thus the outcome of the allostery in this monomeric enzyme is the same as defined by classical theories for multimeric enzymes: making the enzyme response more efficient if appropriate ligands bind.
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Adasme, Melissa F., Katja L. Linnemann, Sarah Naomi Bolz, Florian Kaiser, Sebastian Salentin, V. Joachim Haupt, and Michael Schroeder. "PLIP 2021: expanding the scope of the protein–ligand interaction profiler to DNA and RNA." Nucleic Acids Research 49, W1 (May 5, 2021): W530—W534. http://dx.doi.org/10.1093/nar/gkab294.
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Abstract With the growth of protein structure data, the analysis of molecular interactions between ligands and their target molecules is gaining importance. PLIP, the protein–ligand interaction profiler, detects and visualises these interactions and provides data in formats suitable for further processing. PLIP has proven very successful in applications ranging from the characterisation of docking experiments to the assessment of novel ligand–protein complexes. Besides ligand–protein interactions, interactions with DNA and RNA play a vital role in many applications, such as drugs targeting DNA or RNA-binding proteins. To date, over 7% of all 3D structures in the Protein Data Bank include DNA or RNA. Therefore, we extended PLIP to encompass these important molecules. We demonstrate the power of this extension with examples of a cancer drug binding to a DNA target, and an RNA–protein complex central to a neurological disease. PLIP is available online at https://plip-tool.biotec.tu-dresden.de and as open source code. So far, the engine has served over a million queries and the source code has been downloaded several thousand times.
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Ben-Shlomo, Izhar, and Aaron J. W. Hsueh. "Three’s Company: Two or More Unrelated Receptors Pair with the Same Ligand." Molecular Endocrinology 19, no. 5 (May 1, 2005): 1097–109. http://dx.doi.org/10.1210/me.2004-0451.
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Abstract Intercellular communication relies on signal transduction mediated by extracellular ligands and their receptors. Although the ligand-receptor interaction is usually a two-player event, there are selective examples of one polypeptide ligand interacting with more than one phylogenetically unrelated receptor. Likewise, a few receptors interact with more than one polypeptide ligand, and sometimes with more than one coreceptor, likely through an interlocking of unique protein domains. Phylogenetic analyses suggest that for certain triumvirates, the matching events could have taken place at different evolutionary times. In contrast to a few polypeptide ligands interacting with more than one receptor, we found that many small nonpeptide ligands have been paired with two or more plasma membrane receptors, nuclear receptors, or channels. The observation that many small ligands are paired with more than one receptor type highlights the utilitarian use of a limited number of cellular components during metazoan evolution. These conserved ligands are ubiquitous cell metabolites likely favored by natural selection to establish novel regulatory networks. They likely possess structural features useful for designing agonistic and antagonistic drugs to target diverse receptors.
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Koizumi, Atsuya, Takuya Hasegawa, Atsushi Itadani, Kenji Toda, Taoyun Zhu, and Mineo Sato. "A new lanthanum(III) complex containing acetylacetone and 1H-imidazole." Acta Crystallographica Section E Crystallographic Communications 73, no. 11 (October 20, 2017): 1739–42. http://dx.doi.org/10.1107/s205698901701461x.
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In the title complex, diaqua(1H-imidazole-κN3)(nitrato-κ2O,O′)bis(4-oxopent-2-en-2-olato-κ2O,O′)lanthanum(III), [La(C5H7O2)2(NO3)(C3H4N2)(H2O)2], the La atom is coordinated by eight O atoms of two acetylacetonate (acac) anions acting as bidentate ligands, two water molecule as monodentate ligands, one nitrate anions as a bidentate ligand and one N atom of an imidazolate (ImH) molecule as a monodentate ligand. Thus, the coordination number of the La atom is nine in a monocapped square antiprismatic polyhedron. There are three types of intermolecular hydrogen bonds between ligands, the first involving nitrate–water O...H—O interactions running along the [001] direction, the second involving acac–water O...H—O interactions along the [010] direction and the third involving an Im–nitrate N—H...O interaction along the [100] direction (five interactions of this type). Thus, an overall one-dimensional network structure is generated. The molecular plane of an ImH molecule is almost parallel to that of a nitrate ligand, making an angle of only 6.04 (12)°. Interestingly, the ImH plane is nearly perpendicular to the planes of two neighbouring acac ligands.
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Monaco, Regina R. "Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation." Journal of Nucleic Acids 2010 (2010): 1–4. http://dx.doi.org/10.4061/2010/702317.
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The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to accommodate a variety of ligands in this manner has been well studied. Proposed mechanistic steps along this pathway for the classical intercalator ethidium have been discussed in the literature. Some previous studies indicate that the creation of an intercalation site may occur spontaneously, with the energy for this interaction arising either from solvent collisions or soliton propagation along the helical axis. A subsequent 1D diffusional search by the ligand along the helical axis of the DNA will allow the ligand entry to this intercalation site from its external, electrostatically stabilized position. Other mechanistic studies show that ethidium cation participates in the creation of the site, as a ligand interacting closely with the external surface of the DNA can cause unfavorable steric interactions depending on the ligands' orientation, which are relaxed during the creation of an intercalation site. Briefly, such a site is created by the lengthening of the DNA molecule via bond rotation between the sugars and phosphates along the DNA backbone, causing an unwinding of the dsDNA itself and separation between the adjacent base pairs local to the position of the ligand, which becomes the intercalation site. Previous experimental measurements of this interaction measure the enthalpic cost of this part of the mechanism to be about −8 kcal/mol. This paper reports the observation, during a computational study, of the spontaneous opening of an intercalation site in response to the presence of a single ethidium cation molecule in an externally bound configuration. The concerted motions between this ligand and the host, a dsDNA decamer, are clear. The dsDNA decamer AGGATGCCTG was studied; the central site was the intercalation site.
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Merugu, Ramchander, Uttam Kumar Neerudu, Karunakar Dasa, and Kalpana V. Singh. "Molecular docking studies of deacetylbisacodyl with intestinal sucrase-maltase enzyme." International Journal of Advances in Scientific Research 2, no. 12 (January 1, 2017): 191. http://dx.doi.org/10.7439/ijasr.v2i12.3821.
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Molecular docking of sucrase-isomaltase with ligand deacetylbisacodyl when subjected to docking analysis using docking server, predicted in-silico result with a free energy of -3.36 Kcal/mol which was agreed well with physiological range for protein-ligand interaction, making bisacodyl probable potent anti-isomaltase molecule. According to docking server Inhibition constant is 5.98Mm. which predicts that the ligand is going to inhibits enzyme and result in a clinically relevant drug interaction with a substrate for the enzyme. Hydrogen bond with bond length 3.45is formed between Pro 64 (A) of target and of ligand, which is again indicative of the docking between target and ligand. Excellent electrostatic interactions of polar, hydrophobic, pi-pi and Van der walls are observed. The proteinligand interaction study showed 6 amino acid residues interaction with the ligand.
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Pippal, Jyotsna B., Yizhou Yao, Fraser M. Rogerson, and Peter J. Fuller. "Structural and Functional Characterization of the Interdomain Interaction in the Mineralocorticoid Receptor." Molecular Endocrinology 23, no. 9 (September 1, 2009): 1360–70. http://dx.doi.org/10.1210/me.2009-0032.
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Abstract The mineralocorticoid receptor (MR) plays a central role in electrolyte homeostasis and in cardiovascular disease. We have previously reported a ligand-dependent N/C-interaction in the MR. In the present study we sought to fully characterize the MR N/C-interaction. By using a range of natural and synthetic MR ligands in a mammalian two-hybrid assay we demonstrate that in contrast to aldosterone, which strongly induces the interaction, the physiological ligands deoxycorticosterone and cortisol weakly promote the interaction but predominantly inhibit the aldosterone-mediated N/C-interaction. Similarly, progesterone and dexamethasone antagonize the interaction. In contrast, the synthetic agonist 9α-fludrocortisol robustly induces the interaction. The ability of the N/C interaction to discriminate between MR agonists suggests a subtle conformational difference in the ligand-binding domain induced by these agonists. We also demonstrate that the N/C interaction is not cell specific, consistent with the evidence from a glutathione-S-transferase pull-down assay, of a direct protein-protein interaction between the N- and C-terminal domains of the MR. Examination of a panel of deletions in the N terminus suggests that several regions may be critical to the N/C-interaction. These studies have identified functional differences between physiological MR ligands, which suggest that the ligand-specific dependence of the N/C-interaction may contribute to the differential activation of the MR that has been reported in vivo.
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Burlakov, Victor M., and Alain Goriely. "Ligand-Assisted Growth of Nanowires from Solution." Applied Sciences 11, no. 16 (August 20, 2021): 7641. http://dx.doi.org/10.3390/app11167641.
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We consider the development of ligand-assisted growth processes for generating shape-anisotropic nanomaterials. Using statistical mechanics, we analyze the conditions under which ligand-assisted growth of shape-anisotropic crystalline nanomaterials from solution can take place. Depending on ligand-facet interaction energy and crystal facet area, molecular ligands can form compact layers on some facets leaving other facets free. The growth process is then restricted to free facets and may result in significant anisotropy in crystal shape. Our study uncovers the conditions for ligand-assisted growth of nanoplatelets and nanowires from isotropic or anisotropic seed nanocrystals of cuboid shape. We show that in contrast to nanoplatelets, ligand-assisted growth of nanowires requires certain anisotropy in the ligand-facet interaction energy.
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Mehta, Simpi, and Seema R. Pathak. "INSILICO DRUG DESIGN AND MOLECULAR DOCKING STUDIES OF NOVEL COUMARIN DERIVATIVES AS ANTI-CANCER AGENTS." Asian Journal of Pharmaceutical and Clinical Research 10, no. 4 (April 1, 2017): 335. http://dx.doi.org/10.22159/ajpcr.2017.v10i4.16826.
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Objective: Cancer is the major worldwide problem. It arises due to uncontrolled growth of cells. In the present study a series of novel coumarin derivatives were designed and computationallyoptimized to investigate the interaction between designed ligands and 10 pdb files of five selected proteins. The objective here was to analyse in silico anticancerous activity of designed ligands to reduce cost and time for getting novel anticancerous drug with minimum side effects.Methods: Docking studies were performed to find outmaximum interaction between designed ligands and selected five proteins using Schrondinger software Maestro. Capecitabin has been used as reference compound. Structures of selected proteins were downloaded from protein data bank.Results: All the designed ligands showed mild to excellent binding with proteins.Most of the ligands exhibited better interaction compared to reference compoundcapacitabin with all pdb files. Some of designed ligands amongst (1-7) showed excellent docking score with all pdb files(2v5z, 2v60, 2v61) ofAmine oxidase. Conclusion: All the designed ligands were docked with ten pdb files of five different proteins and it was found that out of seven designed ligand, ligand 4 showed best binding (docking score -10.139 ) with pdb 2v5z of protein Amine oxidase. Docked ligand cavity of ligand 4 showed important hydrophobic/non polar residues such asIle199,Ile316,Trp119,Phe168,Ile198,Cys172,Tyr188,Tyr398,Tyr435,Phe343,Tyr60,Leu328,Leu171 and showed pi-pi interaction with Tyr326.Further wet lab studies are continued in our laboratory to confirm and find out efficiency and activity of target compounds.Keywords: Docking, Mono Amine Oxidase, Coumarin derivatives, Anticancerous activity, binding energy, Ramachandran Plot, Hydrophobic residue.
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Housaindokht, Mohammad R., Mahmood Bahrololoom, Shirin Tarighatpoor, and Ali A. Mossavi-Movahedi. "An approach based on diffusion to study ligand-macromolecule interaction." Acta Biochimica Polonica 49, no. 3 (September 30, 2002): 703–7. http://dx.doi.org/10.18388/abp.2002_3779.
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A new approach has been developed to study binding of a ligand to a macromolecule based on the diffusion process. In terms of the Fick's first law, the concentration of free ligand in the presence of a protein can be determined by the measurement of those ligands which are diffused out. This method is applied to the study of binding of methyl-orange to lysozyme in phosphate buffer of pH 6.2, at 30 degrees C. The binding isotherm was determined initially, followed by application of the Hill equation to the data obtained, then binding constant and binding capacity were estimated.
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Tetteh, Samuel, and Ruphino Zugle. "Theoretical Study of Terminal Vanadium(V) Chalcogenido Complexes Bearing Chlorido and Methoxido Ligands." Journal of Chemistry 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/6796321.
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Solvent (methanol) coordinated vanadium(V) chalcogenido complexes bearing chlorido and methoxido ligands have been studied computationally by means of density functional (DFT) methods. The gas phase complexes were fully optimized using B3LYP/GEN functionals with 6-31+G⁎⁎ and LANL2DZ basis sets. The optimized complexes show distorted octahedral geometries around the central vanadium atom. The ligand pπ-vanadium dπ interactions were analyzed by natural bond order (NBO) and natural population analyses (NPA). These results show strong stabilization of the V=O bond as was further confirmed by the analyses of the frontier molecular orbitals (FMOs). Second-order perturbation analyses also revealed substantial delocalization of lone pair electrons from the oxido ligand into vacant non-Lewis (Rydberg) orbitals as compared to the sulfido and seleno analogues. These results show significant ligand-to-metal charge transfer (LMCT) interactions. Full interaction map (FIM) of the reference complex confirms hydrogen bond interactions involving the methanol (O-H) and the chlorido ligand.
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Andjelkovic, Darko, Ruzica Nikolic, Dejan Markovic, Tatjana Andjelkovic, Gordana Kocic, Zoran Todorovic, and Aleksandar Bojic. "Chromium interaction with O-donor humic-like ligands using electrospray-ionization mass spectrometry." Journal of the Serbian Chemical Society 78, no. 1 (2013): 137–54. http://dx.doi.org/10.2298/jsc120320071a.
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The study of the interaction of chromium with O-donor humic-like ligands is performed by electrospray-ionization mass spectrometry (ESI-MS) and ultraviolet/visible (UV/VIS) spectrophotometry. Heterogeneity of functional groups justifies the use of model compounds of humic substances. For studying the interaction of chromium with humic substances as model substances were used benzoic, salicylic, phthalic and citric acid, which include O-donor atoms, also present in heterogenous and polydispersed ligands, such humic and fulvic acids are. The intensity of the interaction is correlated with the acid-base and electron-donor properties, geometric and steric characteristics, and the number and the positions of O-donor atoms in the investigated ligands. UV/Vis data describing chromium interaction with humic-like ligands is placed in correlation with the ESI-MS data of the complexes, both in quantitative and in qualitative terms. UV/VIS spectroscopy and ESI-MS quantification showed a large difference in the informativeness of describing the interaction of chromium(III)-ligand, in favor of ESI-MS technique. ESI-MS technique can be used for quantitative analysis of the system Cr(III)-ligand. ESI-MS ion current chromatograms of 20 ?L loop injections of systems Cr(III)-ligand, indicate a stabile peak and signal integrity.
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Gutfreund, H. "Half a century's experience with protein ligand interaction. Protein interactions." FEBS Letters 313, no. 3 (November 30, 1992): 319–20. http://dx.doi.org/10.1016/0014-5793(92)81219-c.
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Kapp, E. A., S. Daya, and C. G. Whiteley. "Protein-ligand interactions: Interaction of nitrosamines with nicotinic acetylcholine receptor." Biochemical and Biophysical Research Communications 167, no. 3 (March 1990): 1383–92. http://dx.doi.org/10.1016/0006-291x(90)90676-e.
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Hemmingsen, Lars, Ulf Ryde, and Rogert Bauer. "Nuclear Quadrupole Interactions in Cadmium Complexes: Semiempirical and ab initio Calculations." Zeitschrift für Naturforschung A 54, no. 6-7 (July 1, 1999): 422–30. http://dx.doi.org/10.1515/zna-1999-6-713.
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Abstract Semiempirical calculations, based on the so-called angular overlap model, have been compared with ab initio methods (MP2) for the calculation of nuclear quadrupole interactions (NQI’s) in cadmium complexes with biologically relevant ligands (H2O, OH-, cysteinate, carboxylate, and imidazole). The assumptions on which the semiempirical model is based have been tested and the comparison indicates that: 1) A change in the Cd-ligand bond length by 0.1 A may change the electric field gradient (EFG) by about 0.2 a. u.. A simple scheme to incorporate such effects in the semiempirical method is suggested. 2) The effect of ligand-ligand interactions is up to about 0.2 a. u. for the largest diagonal element of the EFG tensor for the tested complexes, and such effects can significantly influence the so-called asymmetry parameter. 3) The position of non-coordinating atoms on the ligands can in some cases (e. g. the hydrogen atoms of water) significantly influence the EFG. The combined effect of non-coordinating atoms and ligand-ligand interactions may cause deviations of up to 0.35 a.u. between ab initio and the semiempirical calculations. 4) In the semiempirical model each ligand is characterised by one parameter, the so-called partial nuclear quadrupole interaction. This parameter has been evaluated by ab initio calculations, and agreement was found within about 0.2 a. u. (≈ 40 Mrad/s) for all ligands except imidazole. 5) A change in the coordination number from 2 to 6 may change the partial NQI by about 0.3 a. u.
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Hutchens, T. W., and J. O. Porath. "Protein recognition of immobilized ligands: promotion of selective adsorption." Clinical Chemistry 33, no. 9 (September 1, 1987): 1502–8. http://dx.doi.org/10.1093/clinchem/33.9.1502.
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Abstract We are using simple immobilized ligands to evaluate the biochemistry and mechanisms of selective, high-affinity, protein adsorption events. Several specific means have recently been developed to more selectively utilize the favorable entropy changes associated with the displacement of protein-bound water during the formation and stabilization of protein-ligand recognition events. For protein and peptide immobilization these include, besides hydrophobic interaction, for example, metal ion, pi-electron-mediated, and thiophilic interactions. This latter type of protein-ligand recognition process represents a previously unrecognized interaction mechanism of considerable selectivity, affinity, and utility. Specific examples of the above-mentioned principles and protein fractionations include (a) thiophilic adsorption of immunoglobulins to achieve immunoglobulin-free serum for in vitro production and purification of monoclonal antibodies and (b) urea-induced binding of estrogen-receptor proteins to immobilized DNA. The interaction mechanisms are discussed in terms of the molecular architecture of protein surfaces. We present possibilities for the further utilization of these immobilized ligands and their associated proteins in the areas of clinical biochemistry and immunology.
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Stylianou, Marios, Anastasios D. Keramidas, and Chryssoula Drouza. "pH-Potentiometric Investigation towards Chelating Tendencies ofp-Hydroquinone and Phenol Iminodiacetate Copper(II) Complexes." Bioinorganic Chemistry and Applications 2010 (2010): 1–8. http://dx.doi.org/10.1155/2010/125717.
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Copper ions in the active sites of several proteins/enzymes interact with phenols and quinones, and this interaction is associated to the reactivity of the enzymes. In this study the speciation of theCu2+with iminodiacetic phenolate/hydroquinonate ligands has been examined by pH-potentiometry. The results reveal that the iminodiacetic phenol ligand forms mononuclear complexes withCu2+at acidic and alkaline pHs, and a binuclearOphenolate-bridged complex at pH range from 7 to 8.5. The binucleating hydroquinone ligand forms only 2 : 1 metal to ligand complexes in solution. The pK values of the protonation of the phenolate oxygen of the two ligands are reduced about 2 units after complexation with the metal ion and are close to the pK values for the copper-interacting tyrosine phenol oxygen in copper enzymes.
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Kaiser, Anette, and Irene Coin. "Capturing Peptide–GPCR Interactions and Their Dynamics." Molecules 25, no. 20 (October 15, 2020): 4724. http://dx.doi.org/10.3390/molecules25204724.
Full textAbstract:
Many biological functions of peptides are mediated through G protein-coupled receptors (GPCRs). Upon ligand binding, GPCRs undergo conformational changes that facilitate the binding and activation of multiple effectors. GPCRs regulate nearly all physiological processes and are a favorite pharmacological target. In particular, drugs are sought after that elicit the recruitment of selected effectors only (biased ligands). Understanding how ligands bind to GPCRs and which conformational changes they induce is a fundamental step toward the development of more efficient and specific drugs. Moreover, it is emerging that the dynamic of the ligand–receptor interaction contributes to the specificity of both ligand recognition and effector recruitment, an aspect that is missing in structural snapshots from crystallography. We describe here biochemical and biophysical techniques to address ligand–receptor interactions in their structural and dynamic aspects, which include mutagenesis, crosslinking, spectroscopic techniques, and mass-spectrometry profiling. With a main focus on peptide receptors, we present methods to unveil the ligand–receptor contact interface and methods that address conformational changes both in the ligand and the GPCR. The presented studies highlight a wide structural heterogeneity among peptide receptors, reveal distinct structural changes occurring during ligand binding and a surprisingly high dynamics of the ligand–GPCR complexes.
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Singh, Omkar, Kunal Sawariya, and Polamarasetty Aparoy. "Graphlet signature-based scoring method to estimate protein–ligand binding affinity." Royal Society Open Science 1, no. 4 (December 2014): 140306. http://dx.doi.org/10.1098/rsos.140306.
Full textAbstract:
Over the years, various computational methodologies have been developed to understand and quantify receptor–ligand interactions. Protein–ligand interactions can also be explained in the form of a network and its properties. The ligand binding at the protein-active site is stabilized by formation of new interactions like hydrogen bond, hydrophobic and ionic. These non-covalent interactions when considered as links cause non-isomorphic sub-graphs in the residue interaction network. This study aims to investigate the relationship between these induced sub-graphs and ligand activity. Graphlet signature-based analysis of networks has been applied in various biological problems; the focus of this work is to analyse protein–ligand interactions in terms of neighbourhood connectivity and to develop a method in which the information from residue interaction networks, i.e. graphlet signatures, can be applied to quantify ligand affinity. A scoring method was developed, which depicts the variability in signatures adopted by different amino acids during inhibitor binding, and was termed as GSUS (graphlet signature uniqueness score). The score is specific for every individual inhibitor. Two well-known drug targets, COX-2 and CA-II and their inhibitors, were considered to assess the method. Residue interaction networks of COX-2 and CA-II with their respective inhibitors were used. Only hydrogen bond network was considered to calculate GSUS and quantify protein–ligand interaction in terms of graphlet signatures. The correlation of the GSUS with pIC 50 was consistent in both proteins and better in comparison to the Autodock results. The GSUS scoring method was better in activity prediction of molecules with similar structure and diverse activity and vice versa. This study can be a major platform in developing approaches that can be used alone or together with existing methods to predict ligand affinity from protein–ligand complexes.
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Fu, Yi, Ji Zhao, and Zhiguo Chen. "Insights into the Molecular Mechanisms of Protein-Ligand Interactions by Molecular Docking and Molecular Dynamics Simulation: A Case of Oligopeptide Binding Protein." Computational and Mathematical Methods in Medicine 2018 (December 4, 2018): 1–12. http://dx.doi.org/10.1155/2018/3502514.
Full textAbstract:
Protein-ligand interactions are a necessary prerequisite for signal transduction, immunoreaction, and gene regulation. Protein-ligand interaction studies are important for understanding the mechanisms of biological regulation, and they provide a theoretical basis for the design and discovery of new drug targets. In this study, we analyzed the molecular interactions of protein-ligand which was docked by AutoDock 4.2 software. In AutoDock 4.2 software, we used a new search algorithm, hybrid algorithm of random drift particle swarm optimization and local search (LRDPSO), and the classical Lamarckian genetic algorithm (LGA) as energy optimization algorithms. The best conformations of each docking algorithm were subjected to molecular dynamic (MD) simulations to further analyze the molecular mechanisms of protein-ligand interactions. Here, we analyze the binding energy between protein receptors and ligands, the interactions of salt bridges and hydrogen bonds in the docking region, and the structural changes during complex unfolding. Our comparison of these complexes highlights differences in the protein-ligand interactions between the two docking methods. It also shows that salt bridge and hydrogen bond interactions play a crucial role in protein-ligand stability. The present work focuses on extracting the deterministic characteristics of docking interactions from their dynamic properties, which is important for understanding biological functions and determining which amino acid residues are crucial to docking interactions.