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Journal articles on the topic 'Binding kinetics'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

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1

Bernetti, Mattia, Matteo Masetti, Walter Rocchia, and Andrea Cavalli. "Kinetics of Drug Binding and Residence Time." Annual Review of Physical Chemistry 70, no. 1 (June 14, 2019): 143–71. http://dx.doi.org/10.1146/annurev-physchem-042018-052340.

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The kinetics of drug binding and unbinding is assuming an increasingly crucial role in the long, costly process of bringing a new medicine to patients. For example, the time a drug spends in contact with its biological target is known as residence time (the inverse of the kinetic constant of the drug-target unbinding, 1/ koff). Recent reports suggest that residence time could predict drug efficacy in vivo, perhaps even more effectively than conventional thermodynamic parameters (free energy, enthalpy, entropy). There are many experimental and computational methods for predicting drug-target residence time at an early stage of drug discovery programs. Here, we review and discuss the methodological approaches to estimating drug binding kinetics and residence time. We first introduce the theoretical background of drug binding kinetics from a physicochemical standpoint. We then analyze the recent literature in the field, starting from the experimental methodologies and applications thereof and moving to theoretical and computational approaches to the kinetics of drug binding and unbinding. We acknowledge the central role of molecular dynamics and related methods, which comprise a great number of the computational methods and applications reviewed here. However, we also consider kinetic Monte Carlo. We conclude with the outlook that drug (un)binding kinetics may soon become a go/no go step in the discovery and development of new medicines.

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2

Borisov, D. V., and A. V. Veselovsky. "Ligand-receptor binding kinetics in drug design." Biomeditsinskaya Khimiya 66, no. 1 (January 2020): 42–53. http://dx.doi.org/10.18097/pbmc20206601042.

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Traditionally, the thermodynamic values of affinity are considered as the main criterion for the development of new drugs. Usually, these values for drugs are measured in vitro at steady concentrations of the receptor and ligand, which are differed from in vivo environment. Recent studies have shown that the kinetics of the process of drug binding to its receptor make significant contribution in the drug effectiveness. This has increased attention in characterizing and predicting the rate constants of association and dissociation of the receptor ligand at the stage of preclinical studies of drug candidates. A drug with a long residence time can determine ligand-receptor selectivity (kinetic selectivity), maintain pharmacological activity of the drug at its low concentration in vivo. The paper discusses the theoretical basis of protein-ligand binding, molecular determinants that control the kinetics of the drug-receptor binding. Understanding the molecular features underlying the kinetics of receptor-ligand binding will contribute to the rational design of drugs with desired properties.

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3

Kiger, Laurent, Julien Uzan, Sylvia Dewilde, Thorsten Burmester, Thomas Hankeln, Luc Moens, Djemel Hamdane, Veronique Baudin-Creuza, and Michael Marden. "Neuroglobin Ligand Binding Kinetics." IUBMB Life 56, no. 11 (November 2004): 709–19. http://dx.doi.org/10.1080/15216540500037711.

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4

Singh, Arunima. "RNA-binding protein kinetics." Nature Methods 18, no. 4 (April 2021): 335. http://dx.doi.org/10.1038/s41592-021-01122-6.

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5

Ferruz, Noelia, and Gianni De Fabritiis. "Binding Kinetics in Drug Discovery." Molecular Informatics 35, no. 6-7 (May 27, 2016): 216–26. http://dx.doi.org/10.1002/minf.201501018.

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6

Hall, Denver G. "Relaxation kinetics of ion binding." Journal of the Chemical Society, Faraday Transactions 86, no. 4 (1990): 639. http://dx.doi.org/10.1039/ft9908600639.

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7

Gushimana, Y., B. Doepner, E. Martinez-Hackert, and G. Ilgenfritz. "Kinetics of quinine-deuterohemin binding." Biophysical Chemistry 47, no. 2 (August 1993): 153–62. http://dx.doi.org/10.1016/0301-4622(93)85033-e.

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8

Barril, Xavier, and Helena Danielsson. "Binding kinetics in drug discovery." Drug Discovery Today: Technologies 17 (October 2015): 35–36. http://dx.doi.org/10.1016/j.ddtec.2015.10.011.

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9

McNeely, Patrick M., Andrea N. Naranjo, Kimberly Forsten-Williams, and Anne Skaja Robinson. "A2AR Binding Kinetics in the Ligand Depletion Regime." SLAS DISCOVERY: Advancing the Science of Drug Discovery 22, no. 2 (September 27, 2016): 166–75. http://dx.doi.org/10.1177/1087057116667256.

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Ligand binding plays a fundamental role in stimulating the downstream signaling of membrane receptors. Here, ligand-binding kinetics of the full-length human adenosine A2A receptor (A2AR) reconstituted in detergent micelles were measured using a fluorescently labeled ligand via fluorescence anisotropy. Importantly, to optimize the signal-to-noise ratio, these experiments were conducted in the ligand depletion regime. In the ligand depletion regime, the assumptions used to determine analytical solutions for one-site binding models for either one or two ligands in competition are no longer valid. We therefore implemented a numerical solution approach to analyze kinetic binding data as experimental conditions approach the ligand depletion regime. By comparing the results from the numerical and the analytical solutions, we highlight the ligand-receptor ratios at which the analytical solution begins to lose predictive accuracy. Using the numerical solution approach, we determined the kinetic rate constants of the fluorescent ligand, FITC-APEC, and those for three unlabeled ligands using competitive association experiments. The association and dissociation rate constants of the unlabeled ligands determined from the competitive association experiments were then independently validated using competitive dissociation data. Based on this study, a numerical solution is recommended to determine kinetic ligand-binding parameters for experiments conducted in the ligand-depletion regime.

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10

Rundell, K. W., P. C. Tullson, and R. L. Terjung. "Altered kinetics of AMP deaminase by myosin binding." American Journal of Physiology-Cell Physiology 263, no. 2 (August 1, 1992): C294—C299. http://dx.doi.org/10.1152/ajpcell.1992.263.2.c294.

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AMP deaminase catalyzes the deamination of AMP to inosine 5'-monophosphate (IMP) and ammonia. Factors controlling the enzyme in muscle can rapidly promote high rates of IMP formation when ATP utilization exceeds supply. We evaluated whether binding of AMP deaminase to myosin, which occurs during intense contraction conditions, alters the kinetic behavior of the enzyme. Reaction kinetics of myosin-bound and free AMP deaminase were evaluated. Reaction kinetics of the free enzyme yielded a near-linear double-reciprocal plot with an expected Km of approximately 1 mM AMP concentration (AMP). In contrast, reaction kinetics of AMP deaminase became bimodal when bound to myosin. At [AMP] less than 0.15 mM, a high-affinity Km (0.05-0.10 mM) with maximal velocity approximately 20% that of free enzyme was evident. At [AMP] greater than 0.15 mM, the Km and maximal velocity values were similar to that of the free enzyme. The 10- to 20-fold higher affinity Km would allow for a higher rate of AMP deamination at the low [AMP] found physiologically. AMP deaminase binding to myosin also induced a marked resistance to orthophosphate inhibition (10 mM) in the presence of 50 microM ADP. Results were similar for purified preparations of AMP deaminase bound to myosin subfragment 2 and crude extracts obtained from contracting muscle. Our results add further support to the hypothesis that AMP deaminase binding to myosin serves an important role in control of enzyme activity in contracting muscle.

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11

Boonserm, Patamalai, Songchan Puthong, Sajee Noitang, Thanaporn Wichai, Pongsak Khunrae, Kittinan Komolpis, and Sarintip Sooksai. "Kinetics of Binding Interaction between Norfloxacin and Monoclonal Antibody Using Surface Plasmon Resonance." International Journal of Pharma Medicine and Biological Sciences 9, no. 2 (2020): 81–86. http://dx.doi.org/10.18178/ijpmbs.9.2.81-86.

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12

BOONKITTICHAROEN, V., and K. LAOHATHAI. "Variables influencing cell binding assays for antibody binding kinetics." Nuclear Medicine Communications 14, no. 1 (1993): 70–75. http://dx.doi.org/10.1097/00006231-199301000-00013.

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13

Louis Mege, Jean, Christian Capo, Anne Marie Benoliel, and Pierre Bongrand. "Determination of binding strength and kinetics of binding initiation." Cell Biophysics 8, no. 2 (April 1986): 141–60. http://dx.doi.org/10.1007/bf02788478.

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14

Leckband, Deborah. "Beyond structure: mechanism and dynamics of intercellular adhesion." Biochemical Society Transactions 36, no. 2 (March 20, 2008): 213–20. http://dx.doi.org/10.1042/bst0360213.

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This review summarizes findings from multiple complementary quantitative investigations of adhesion by classical cadherins. The systems investigated range from single molecules to cells, and the approaches used quantify the kinetics, energetics and mechanical strengths of cadherin bonds. The cumulative results demonstrate that cadherins adhere via a multistage binding mechanism that involves multiple extracellular domains. In kinetic measurements of cell adhesion, cell pairs first form a low-probability-binding state with fast kinetics. This is followed by a lag and a slow transition to a second, high-probability, binding state. This two-stage process is independent of the cytoplasmic domain. Studies with domain-deletion mutants demonstrate that the N-terminal domains are required for the first, fast, weak binding. However, the full-ectodomain and EC3 (extracellular repeat 3), in particular, are required to form the second, high-probability, binding state, which is characterized by slow dissociation kinetics and much stronger adhesive bonds. Together, these different studies reveal a more complex multistage binding mechanism than was predicted by structural models.

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15

Shimizu, Yuji, Kazumasa Ogawa, and Masaharu Nakayama. "Characterization of Kinetic Binding Properties of Unlabeled Ligands via a Preincubation Endpoint Binding Approach." Journal of Biomolecular Screening 21, no. 7 (July 10, 2016): 729–37. http://dx.doi.org/10.1177/1087057116652065.

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The dissociation rates of unlabeled drugs have been well studied by kinetic binding analyses. Since kinetic assays are laborious, we developed a simple method to determine the kinetic binding parameters of unlabeled competitors by a preincubation endpoint assay. The probe binding after preincubation of a competitor can be described by a single equation as a function of time. Simulations using the equation revealed the degree of IC50 change induced by preincubation of a competitor depended on the dissociation rate koff of the competitor but not on the association rate kon. To validate the model, an in vitro binding assay was performed using a smoothened receptor (SMO) and [3H]TAK-441, a SMO antagonist. The equilibrium dissociation constants (KI) and koff of SMO antagonists determined by globally fitting the model to the concentration–response curves obtained with and without 24 h preincubation correlated well with those determined by other methods. This approach could be useful for early-stage optimization of drug candidates by enabling determination of binding kinetics in a high-throughput manner because it does not require kinetic measurements, an intermediate washout step during the reaction, or prior determination of competitors’ KI values.

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16

de Lange, Willem J., Adrian C. Grimes, Laura F. Hegge, and J. Carter Ralphe. "Ablation of cardiac myosin–binding protein-C accelerates contractile kinetics in engineered cardiac tissue." Journal of General Physiology 141, no. 1 (December 31, 2012): 73–84. http://dx.doi.org/10.1085/jgp.201210837.

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Hypertrophic cardiomyopathy (HCM) caused by mutations in cardiac myosin–binding protein-C (cMyBP-C) is a heterogenous disease in which the phenotypic presentation is influenced by genetic, environmental, and developmental factors. Though mouse models have been used extensively to study the contractile effects of cMyBP-C ablation, early postnatal hypertrophic and dilatory remodeling may overshadow primary contractile defects. The use of a murine engineered cardiac tissue (mECT) model of cMyBP-C ablation in the present study permits delineation of the primary contractile kinetic abnormalities in an intact tissue model under mechanical loading conditions in the absence of confounding remodeling events. We generated mechanically integrated mECT using isolated postnatal day 1 mouse cardiac cells from both wild-type (WT) and cMyBP-C–null hearts. After culturing for 1 wk to establish coordinated spontaneous contraction, we measured twitch force and Ca2+ transients at 37°C during pacing at 6 and 9 Hz, with and without dobutamine. Compared with WT, the cMyBP-C–null mECT demonstrated faster late contraction kinetics and significantly faster early relaxation kinetics with no difference in Ca2+ transient kinetics. Strikingly, the ability of cMyBP-C–null mECT to increase contractile kinetics in response to adrenergic stimulation and increased pacing frequency were severely impaired. We conclude that cMyBP-C ablation results in constitutively accelerated contractile kinetics with preserved peak force with minimal contractile kinetic reserve. These functional abnormalities precede the development of the hypertrophic phenotype and do not result from alterations in Ca2+ transient kinetics, suggesting that alterations in contractile velocity may serve as the primary functional trigger for the development of hypertrophy in this model of HCM. Our findings strongly support a mechanism in which cMyBP-C functions as a physiological brake on contraction by positioning myosin heads away from the thin filament, a constraint which is removed upon adrenergic stimulation or cMyBP-C ablation.

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17

Stein, Julian A. C., Alan Ianeselli, and Dieter Braun. "Kinetic Microscale Thermophoresis for Simultaneous Measurement of Binding Affinity and Kinetics." Angewandte Chemie International Edition 60, no. 25 (May 11, 2021): 13988–95. http://dx.doi.org/10.1002/anie.202101261.

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18

Stein, Julian A. C., Alan Ianeselli, and Dieter Braun. "Kinetic Microscale Thermophoresis for Simultaneous Measurement of Binding Affinity and Kinetics." Angewandte Chemie 133, no. 25 (May 11, 2021): 14107–14. http://dx.doi.org/10.1002/ange.202101261.

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19

Saleh, Sanaa Rabie, and Ahmed Daham Wiheeb. "Kinetic Study of Carbon Dioxide Reaction with Binding Organic Liquids." TJES Vol26 No.1 2019 26, no. 1 (March 3, 2019): 26–32. http://dx.doi.org/10.25130/tjes.26.1.04.

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Binding organic liquids are a strong base of amidine have been used for CO2 capture. Up to now, there is no known datum on the reaction kinetics of CO2 with 1,5-Diazabicyclo[4.3.0]non-5-ene (DBN). In this paper, Kinetics of reaction between CO2 and DBN/MDEA in 1-Pentanol were performed utilizing the stirred cell reactor with DBN concentration (2 – 2.9 M) and at room temperature. The reaction path was qualified using zwitterion and the termolecular mechanism. From the kinetic datum with DBN concentrations (2 – 2.9 M), it was found that the capturing process happen in a fast reaction system with a second-order reaction kinetics of DBN/MDEA and first order with CO2. In addition, CO2 absorption was achieved using gas – liquid contact system. CO2 absorption rate was (2×10^(-5)-2.8 × 10^(-5) kmol⁄m^2 .sec) at DBN concentration (2 – 2.9 M). Finally, it is known that DBN/MDEA/1-Pentanol/CO2 system is easily switchable and can be used both CO2 capture and for other applications that require rapid change of medium from nonionic to ionic liquid.

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20

GIBSON, QUENTIN H. "Kinetics of ligand binding to haemoproteins." Biochemical Society Transactions 18, no. 1 (February 1, 1990): 1–6. http://dx.doi.org/10.1042/bst0180001.

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21

Cologne, John B., Paul M. Mendelman, and Donald O. Chaffin. "Statistical comparison of ligand-binding kinetics." Statistics in Medicine 8, no. 7 (July 1989): 871–81. http://dx.doi.org/10.1002/sim.4780080711.

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22

Cologne, J. B., P. M. Mendelman, D. O. Chaffin, G. Dunn, John B. Cologne, Paul M. Mendelman, and Donald O. Chaffin. "Statistical comparisons of ligand-binding kinetics." Statistics in Medicine 9, no. 3 (March 1990): 341–42. http://dx.doi.org/10.1002/sim.4780090317.

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23

Poland, Douglas. "On the kinetics of oligomer binding." Biopolymers 30, no. 13-14 (1990): 1215–30. http://dx.doi.org/10.1002/bip.360301307.

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24

Funaki, Tomoo, Hideo Fukazawa, and Isami Kuruma. "Metabolic Kinetics of Nonproductive Binding Inhibition." Journal of Pharmaceutical Sciences 83, no. 8 (August 1994): 1181–83. http://dx.doi.org/10.1002/jps.2600830820.

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25

Wong, Chung F. "Molecular simulation of drug-binding kinetics." Molecular Simulation 40, no. 10-11 (March 20, 2014): 889–903. http://dx.doi.org/10.1080/08927022.2014.890722.

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26

Hammond, James R. "Modulation of [3H]Nitrobenzylthioinosine Binding Kinetics." Nucleosides and Nucleotides 10, no. 5 (July 1991): 1103–6. http://dx.doi.org/10.1080/07328319108047247.

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27

Rico, Felix, Atsunori Oshima, Yoshinori Fujiyoshi, Peter Hinterdorfer, and Simon Scheuring. "Binding Kinetics of Inter-Connexon Interaction." Biophysical Journal 100, no. 3 (February 2011): 564a. http://dx.doi.org/10.1016/j.bpj.2010.12.3273.

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28

Sadana, Ajit, and Aruna Beela Ram. "Antigen-antibody binding kinetics for biosensors." Applied Biochemistry and Biotechnology 60, no. 2 (August 1996): 123–38. http://dx.doi.org/10.1007/bf02788067.

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29

Quintana, Andrea R., Dan Wang, Joanna E. Forbes, and M. Neal Waxham. "Kinetics of calmodulin binding to calcineurin." Biochemical and Biophysical Research Communications 334, no. 2 (August 2005): 674–80. http://dx.doi.org/10.1016/j.bbrc.2005.06.152.

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30

Clements, J. D., and G. L. Westbrook. "Kinetics of AP5 dissociation from NMDA receptors: evidence for two identical cooperative binding sites." Journal of Neurophysiology 71, no. 6 (June 1, 1994): 2566–69. http://dx.doi.org/10.1152/jn.1994.71.6.2566.

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s1. N-methyl-D-aspartate (NMDA) channels have two agonist binding sites that have similar binding rates for glutamate. However, it is not known whether the dissociation rates at these two sites, and hence their affinities, are similar. The competitive antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), was used to study dissociation kinetics from NMDA receptors in outside-out patches from cultured hippocampal neurons. 2. Rapid steps from AP5 into NMDA produced currents with a sigmoidal activation time course that was limited by AP5 dissociation. Ensemble average currents were well fitted using kinetic models with two identical, cooperative antagonist binding sites per channel. The results suggest that the two NMDA binding sites have similar affinities, but that occupation of one site reduces the affinity of the other. 3. The agonist and antagonist binding kinetics are consistent with an approximately homogeneous population of NMDA channels in cultured hippocampal neurons.

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31

Jing, Wenwen, Ashley Hunt, Nongjian Tao, Fenni Zhang, and Shaopeng Wang. "Simultaneous Quantification of Protein Binding Kinetics in Whole Cells with Surface Plasmon Resonance Imaging and Edge Deformation Tracking." Membranes 10, no. 9 (September 22, 2020): 247. http://dx.doi.org/10.3390/membranes10090247.

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Most drugs work by binding to receptors on the cell surface. Quantification of binding kinetics between drug and membrane protein is an essential step in drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, and both have issues. Surface plasmon resonance (SPR) imaging has been demonstrated for quantification of protein binding to cells with single-cell resolution, but it only senses the bottom of the cell and the signal diminishes with the molecule size. We have discovered that ligand binding to the cell surface is accompanied by a small cell membrane deformation, which can be used to measure the binding kinetics by tracking the cell edge deformation. Here, we report the first integration of SPR imaging and cell edge tracking methods in a single device, and we use lectin interaction as a model system to demonstrate the capability of the device. The integration enables the simultaneous collection of complementary information provided by both methods. Edge tracking provides the advantage of small molecule binding detection capability, while the SPR signal scales with the ligand mass and can quantify membrane protein density. The kinetic constants from the two methods were cross-validated and found to be in agreement at the single-cell level. The variation of observed rate constant between the two methods is about 0.009 s−1, which is about the same level as the cell-to-cell variations. This result confirms that both methods can be used to measure whole-cell binding kinetics, and the integration improves the reliability and capability of the measurement.

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32

Glöckner, Steffen, Khang Ngo, Björn Wagner, Andreas Heine, and Gerhard Klebe. "The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II." Biomolecules 10, no. 4 (March 27, 2020): 509. http://dx.doi.org/10.3390/biom10040509.

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The fluorination of lead-like compounds is a common tool in medicinal chemistry to alter molecular properties in various ways and with different goals. We herein present a detailed study of the binding of fluorinated benzenesulfonamides to human Carbonic Anhydrase II by complementing macromolecular X-ray crystallographic observations with thermodynamic and kinetic data collected with the novel method of kinITC. Our findings comprise so far unknown alternative binding modes in the crystalline state for some of the investigated compounds as well as complex thermodynamic and kinetic structure-activity relationships. They suggest that fluorination of the benzenesulfonamide core is especially advantageous in one position with respect to the kinetic signatures of binding and that a higher degree of fluorination does not necessarily provide for a higher affinity or more favorable kinetic binding profiles. Lastly, we propose a relationship between the kinetics of binding and ligand acidity based on a small set of compounds with similar substitution patterns.

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33

Lolkema, Juke S., and Dirk-Jan Slotboom. "The Hill analysis and co-ion–driven transporter kinetics." Journal of General Physiology 145, no. 6 (May 25, 2015): 565–74. http://dx.doi.org/10.1085/jgp.201411332.

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Interaction of multiple ligands with a protein or protein complex is a widespread phenomenon that allows for cooperativity. Here, we review the use of the Hill equation, which is commonly used to analyze binding or kinetic data, to analyze the kinetics of ion-coupled transporters and show how the mechanism of transport affects the Hill coefficient. Importantly, the Hill analysis of ion-coupled transporters can provide the exact number of transported co-ions, regardless of the extent of the cooperativity in ion binding.

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34

Daniels, Kyle G., Yang Suo, and Terrence G. Oas. "Conformational kinetics reveals affinities of protein conformational states." Proceedings of the National Academy of Sciences 112, no. 30 (July 10, 2015): 9352–57. http://dx.doi.org/10.1073/pnas.1502084112.

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Most biological reactions rely on interplay between binding and changes in both macromolecular structure and dynamics. Practical understanding of this interplay requires detection of critical intermediates and determination of their binding and conformational characteristics. However, many of these species are only transiently present and they have often been overlooked in mechanistic studies of reactions that couple binding to conformational change. We monitored the kinetics of ligand-induced conformational changes in a small protein using six different ligands. We analyzed the kinetic data to simultaneously determine both binding affinities for the conformational states and the rate constants of conformational change. The approach we used is sufficiently robust to determine the affinities of three conformational states and detect even modest differences in the protein’s affinities for relatively similar ligands. Ligand binding favors higher-affinity conformational states by increasing forward conformational rate constants and/or decreasing reverse conformational rate constants. The amounts by which forward rate constants increase and reverse rate constants decrease are proportional to the ratio of affinities of the conformational states. We also show that both the affinity ratio and another parameter, which quantifies the changes in conformational rate constants upon ligand binding, are strong determinants of the mechanism (conformational selection and/or induced fit) of molecular recognition. Our results highlight the utility of analyzing the kinetics of conformational changes to determine affinities that cannot be determined from equilibrium experiments. Most importantly, they demonstrate an inextricable link between conformational dynamics and the binding affinities of conformational states.

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35

Matija, L., J. Jovanović, B. Adnadjević, and Dj Koruga. "Kinetics of Interaction between Fullerol C₆₀(OH)₂₄ and Polyacrylic Hydrogels." Materials Science Forum 494 (September 2005): 555–60. http://dx.doi.org/10.4028/www.scientific.net/msf.494.555.

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In this paper kinetics of binding of fullerol to polyacrylic hydrogel at different temperatures, 298, 308 and 318 K, has been investigated. Time dependences of specific capacity of fullerol binding to hydrogel at defined temperatures are determined. Kinetic curves of specific binding capacity of fullerol for hydrogel are described by equations: t x k t x k x max 1 2 max 1 1+ = and x=k2tn. Rate constants k1 and k2 of the specific fullerol binding capacity at various temperatures are determined. Based on changes in constants k1 and k2 with temperature, kinetic parameters of the investigated process are calculated. Also, due to a great difference in values of kinetic parameters k1 and k2 obtained by varying the temperature, kinetic parameters are determined by using Friedman’s isoconversion method. The values of kinetic parameters based on temperature changes in k2 correspond to the values of kinetic parameters for 9 . 0 » a , while the values of kinetic parameters calculated according to the temperature change in k1, correspond to the Ea values. According to the obtained results it is concluded that the investigated process is controlled by diffusion.

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36

GALLIS, C., B. LEGRAND, and G. TRÉGLIA. "SURFACE ALLOY FORMATION IN THE Cu–Pd(111) SYSTEM: A KTBIM APPROACH." Surface Review and Letters 04, no. 06 (December 1997): 1119–22. http://dx.doi.org/10.1142/s0218625x97001401.

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We study the kinetics of formation and dissolution of surface alloy obtained by depositing one monolayer of Pd on Cu(111) at room temperature. This is performed within the kinetic tight-binding Ising model. We also present the equilibrium segregation isotherm for Pd c Cu 1-c(111) and show the relation between kinetics (surface alloy) and equilibrium (alloy surface) via the local equilibrium concept.

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37

Atkins, William M. "NON-MICHAELIS-MENTEN KINETICS IN CYTOCHROME P450-CATALYZED REACTIONS." Annual Review of Pharmacology and Toxicology 45, no. 1 (September 22, 2005): 291–310. http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.100004.

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The cytochrome P450 monooxygenases (CYPs) are the dominant enzyme system responsible for xenobiotic detoxification and drug metabolism. Several CYP isoforms exhibit non-Michaelis-Menten, or “atypical,” steady state kinetic patterns. The allosteric kinetics confound prediction of drug metabolism and drug-drug interactions, and they challenge the theoretical paradigms of allosterism. Both homotropic and heterotropic ligand effects are now widely documented. It is becoming apparent that multiple ligands can simultaneously bind within the active sites of individual CYPs, and the kinetic parameters change with ligand occupancy. In fact, the functional effect of any specific ligand as an activator or inhibitor can be substrate dependent. Divergent approaches, including kinetic modeling and X-ray crystallography, are providing new information about how multiple ligand binding yields complex CYP kinetics.

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38

TANAKA, Atsushi, and Eiichi HOSHINO. "Calcium-binding parameter of Bacillus amyloliquefaciens α-amylase determined by inactivation kinetics." Biochemical Journal 364, no. 3 (June 15, 2002): 635–39. http://dx.doi.org/10.1042/bj20011436.

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The irreversible thermal inactivation and the thermodynamics of calcium ion binding of Bacillus amyloliquefaciens α-amylase in the absence of substrates were studied. The enzyme inactivation on heating was apparently followed by first-order kinetics. The enzyme was stabilized with an increased concentration of calcium ion and thus the inactivation was highly dependent on the state of calcium binding. The activation parameter for the inactivation suggests an unfolding of the enzyme protein upon heating. Values of both the activation enthalpy and entropy were increased with a higher calcium ion concentration. An inactivation kinetic model is based on the assumption of a two-stage unfolding transition in which the bivalent ion dissociation occurs in the first step followed by the secondary structural unfolding. This simple kinetic model provides both a qualitative and quantitative interpretation of calcium ion binding to the enzyme and its effect on the inactivation properties. The specific approximations of the kinetic model were strictly followed in the analysis to calculate the apparent inactivation rate at each calcium ion concentration in terms of the calcium-binding parameters. The enthalpy and entropy changes for the calcium ion binding were calculated to be −149kJ/mol and −360J·mol−1·K−1 respectively and these values suggest a strong enthalpic affinity for the bivalent ion binding to the enzyme protein. The thermodynamical interpretation attempts to provide clear relations between the terms of an apparent inactivation rate and the calcium binding.

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39

Guo, Dong, Erika J. H. van Dorp, Thea Mulder-Krieger, Jacobus P. D. van Veldhoven, Johannes Brussee, Adriaan P. IJzerman, and Laura H. Heitman. "Dual-Point Competition Association Assay." Journal of Biomolecular Screening 18, no. 3 (October 23, 2012): 309–20. http://dx.doi.org/10.1177/1087057112464776.

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The concept of ligand-receptor binding kinetics is emerging as an important parameter in the early phase of drug discovery. Since the currently used kinetic assays are laborious and low throughput, we developed a method that enables fast and large format screening. It is a so-called dual-point competition association assay, which measures radioligand binding at two different time points in the absence or presence of unlabeled competitors. Specifically, this assay yields the kinetic rate index (KRI), which is a measure for the binding kinetics of the unlabeled ligands screened. As a prototypical drug target, the adenosine A1 receptor (A1R) was chosen for assay validation and optimization. A screen with 35 high-affinity A1R antagonists yielded seven compounds with a KRI value above 1.0, which indicated a relatively slow dissociation from the target. All other compounds had a KRI value below or equal to 1.0, predicting a relatively fast dissociation rate. Several compounds were selected for follow-up kinetic quantifications in classical kinetic assays and were shown to have kinetic rates that corresponded to their KRI values. The dual-point assay and KRI value may have general applicability at other G-protein-coupled receptors, as well as at drug targets from other protein families.

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40

Naber, J. Dirk, and Jack J. S. van Rensen. "Activity of Photosystem II Herbicides Is Related with Their Residence Times at the D 1 Protein." Zeitschrift für Naturforschung C 46, no. 7-8 (August 1, 1991): 575–78. http://dx.doi.org/10.1515/znc-1991-7-812.

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Abstract The reversible binding kinetics of atrazine, diuron and ioxynil were measured via their binding and release parameters during steady state inhibition of electron transport. The parameters were determined in isolated chloroplasts of peas and of triazine-resistant and -susceptible bio types of Chenopodium album using a kinetic model. This model is based on the flash-induced oxygen evolution patterns of isolated broken chloroplasts. It was found that the binding parameters were always significantly higher in the case of an oxidized acceptor quinone complex as compared with a semi-reduced complex. Triazine resistance seems to originate from a significant increase of the release kinetics. The release parameters could be used to calculate the residence times of the herbicides at the D 1 protein. The values of these residence times were always much higher for the herbicides than for Q B; this explains the inhibition of electron transport. The only exception was the residence time of atrazine in the resistant biotype, where the value was close to that of Q B. It is concluded that the “on” kinetics of a compound to its binding environment at the D 1 protein are determined principally by the accessibility of the niche to the compound. The differences in activity between herbicides are mainly due to variations in the release kinetics.

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41

Coletta, M., T. Brittain, and M. Brunori. "Evidence for a kinetic heterogeneity in ligand binding to R-state haemoglobin Kempsey [Asp-G1(99) β→Asn]." Biochemical Journal 238, no. 2 (September 1, 1986): 353–57. http://dx.doi.org/10.1042/bj2380353.

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Thermodynamic and kinetic properties of O2 and CO binding to haemoglobin (Hb) Kempsey [Asp-G1(99) beta----Asn] were investigated and the activation parameters for the two ligands were determined. At every temperature the O2-binding isotherms display a weak co-operativity, n ranging between 1.1 and 1.2, and dissociation kinetics show a single-exponential behaviour. O2-binding kinetics were studied at 25 degrees C by temperature jump and are characterized at each saturation (from Y = 0.31 to Y = 1.0) by two processes, a fast bimolecular one and a slow monomolecular one (tau -1 = 20 s-1), which contributes to approx. 30% of the whole relaxation amplitude at every Y. CO-binding kinetics to Hb Kempsey were followed at several temperatures by flash photolysis and stopped flow. The process is biphasic, as reported elsewhere [Bunn, Wohl, Bradley, Cooley & Gibson (1974) J. Biol. Chem. 249, 7402-7409], and the relative contributions of the two bimolecular rates to the whole process are only slightly affected by temperature. On taking account for the fraction of dimers at every protein concentration, the slow phase corresponds to approx. 50% of the ligand binding to tetramers. Correlation of these results with previous spectroscopic data leads to the hypothesis that the biphasic time course of CO binding may be attributed to alpha/beta heterogeneity of the R-state of tetrameric Hb Kempsey.

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42

Crabbe, M. James C., and Derek Goode. "Nonlinear steady-state kinetics of chloramphenicol acetyltransferase." Biochemistry and Cell Biology 69, no. 9 (September 1, 1991): 630–34. http://dx.doi.org/10.1139/o91-093.

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Steady-state kinetic analysis of chloramphenicol acetyltransferase showed that medium effects (higher temperatures or pH, higher ionic strengths, or lower values for dielectric constant) altered the kinetic behaviour of the enzyme with acetyl-CoA as substrate, but did not significantly affect behaviour with chloramphenicol. This was manifest as an increase in the degree of the rate equation to a 2:2 function. This is interpreted in terms of perturbations to the enzyme at or near the acetyl-CoA binding region of the enzyme.Key words: acetyl coenzyme A, chloramphenicol, antibiotics, enzyme kinetics.

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43

Ganotra, Gaurav K., and Rebecca C. Wade. "Prediction of Drug–Target Binding Kinetics by Comparative Binding Energy Analysis." ACS Medicinal Chemistry Letters 9, no. 11 (October 4, 2018): 1134–39. http://dx.doi.org/10.1021/acsmedchemlett.8b00397.

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44

Bardelle, C., B. Furie, B. C. Furie, and G. E. Gilbert. "Membrane binding kinetics of factor VIII indicate a complex binding process." Journal of Biological Chemistry 268, no. 12 (April 1993): 8815–24. http://dx.doi.org/10.1016/s0021-9258(18)52947-1.

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45

Chambers, H. F., M. J. Sachdeva, and C. J. Hackbarth. "Kinetics of penicillin binding to penicillin-binding proteins of Staphylococcus aureus." Biochemical Journal 301, no. 1 (July 1, 1994): 139–44. http://dx.doi.org/10.1042/bj3010139.

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Reduced affinity of penicillin-binding proteins (PBPs) for binding penicillin has been proposed as a mechanism of beta-lactam antibiotic resistance in staphylococci. Penicillin binding by PBPs of three penicillin-susceptible and two penicillin-resistant strains of Staphylococcus aureus was studied in kinetic assays to determine rate constants, drug concentrations at which PBPs were bound and the relationship between concentrations that bound PBPs and concentrations that inhibited bacterial growth. PBPs 1 and 2 of the resistant strains exhibited slower acylation and more rapid deacylation than susceptible strains. In contrast PBP 4, a naturally low-affinity PBP, was modified such that it exhibited a lower rate of deacylation. The concentrations of penicillin at which modified PBPs were bound correlated with concentrations that inhibited growth of the resistant strains. Acquisition of penicillin resistance in these strains of S. aureus results, at least in part, from structural modifications affecting binding of multiple PBPs and appears to include recruitment of a non-essential PBP, PBP 4.

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46

Chang, Hangil, and Toshiro Fujita. "A kinetic model of the thiazide-sensitive Na-Cl cotransporter." American Journal of Physiology-Renal Physiology 276, no. 6 (June 1, 1999): F952—F959. http://dx.doi.org/10.1152/ajprenal.1999.276.6.f952.

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The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of thiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride; 2) inhibitory effect of chloride on thiazide binding; 3) stimulatory effect of sodium on thiazide binding; 4) combined effects of sodium and chloride on thiazide binding; 5) dependence of sodium influx on extracellular sodium and chloride; and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.

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47

Levels, J. H. M., P. R. Abraham, A. van den Ende, and S. J. H. van Deventer. "Distribution and Kinetics of Lipoprotein-Bound Endotoxin." Infection and Immunity 69, no. 5 (May 1, 2001): 2821–28. http://dx.doi.org/10.1128/iai.69.5.2821-2828.2001.

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ABSTRACT Lipopolysaccharide (LPS), the major glycolipid component of gram-negative bacterial outer membranes, is a potent endotoxin responsible for pathophysiological symptoms characteristic of infection. The observation that the majority of LPS is found in association with plasma lipoproteins has prompted the suggestion that sequestering of LPS by lipid particles may form an integral part of a humoral detoxification mechanism. Previous studies on the biological properties of isolated lipoproteins used differential ultracentrifugation to separate the major subclasses. To preserve the integrity of the lipoproteins, we have analyzed the LPS distribution, specificity, binding capacity, and kinetics of binding to lipoproteins in human whole blood or plasma by using high-performance gel permeation chromatography and fluorescent LPS of three different chemotypes. The average distribution of O111:B4, J5, or Re595 LPS in whole blood from 10 human volunteers was 60% (±8%) high-density lipoprotein (HDL), 25% (±7%) low-density lipoprotein, and 12% (±5%) very low density lipoprotein. The saturation capacity of lipoproteins for all three LPS chemotypes was in excess of 200 μg/ml. Kinetic analysis however, revealed a strict chemotype dependence. The binding of Re595 or J5 LPS was essentially complete within 10 min, and subsequent redistribution among the lipoprotein subclasses occurred to attain similar distributions as O111:B4 LPS at 40 min. We conclude that under simulated physiological conditions, the binding of LPS to lipoproteins is highly specific, HDL has the highest binding capacity for LPS, the saturation capacity of lipoproteins for endotoxin far exceeds the LPS concentrations measured in clinical situations, and the kinetics of LPS association with lipoproteins display chemotype-dependent differences.

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48

Vlot, AJ, SJ Koppelman, JC Meijers, C. Dama, HM van den Berg, BN Bouma, JJ Sixma, and GM Willems. "Kinetics of factor VIII-von Willebrand factor association." Blood 87, no. 5 (March 1, 1996): 1809–16. http://dx.doi.org/10.1182/blood.v87.5.1809.1809.

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Abstract The binding of factor VIII to von Willebrand factor (vWF) is essential for the protection of factor VIII against proteolytic degradation in plasma. We have characterized the binding kinetics of human factor VIII with vWF using a centrifugation binding assay. Purified or plasma vWF was immobilized with a monoclonal antibody (MoAb RU1) covalently linked to Sepharose (Pharmacia LKB Biotechnology, Uppsala, Sweden). Factor VIII was incubated with vWF-RU1-Sepharose and unbound factor VIII was separated from bound factor VIII by centrifugation. The amount of bound factor VIII was determined from the decrease of factor VIII activity in the supernatant. Factor VIII binding to vWF-RU1-Sepharose conformed to the Langmuir model for independent binding sites with a Kd of 0.46 +/- 0.12 nmol/L, and a stoichiometry of 1.3 factor VIII molecules per vWF monomer at saturation, suggesting that each vWF subunit contains a binding site for factor VIII. Competition experiments were performed with a recombinant vWF (deltaA2-rvWF), lacking residues 730 to 910 which contain the epitope for MoAB RU1. DeltaA2-rvWF effectively displaced previously bound factor VIII, confirming that factor VIII binding to vWF-RU1-Sepharose was reversible. To determine the association rate constant (k(on)) and the dissociation rate constant (k(off)), factor VIII was incubated with vWF-RU1-Sepharose for various time intervals. The observed association kinetics conformed to a simple bimolecular association reaction with k(on) = 5.9 +/- 1.9 x 10(6) M(-1) s(-1) and k(off) = 1.6 +/- 1.2 x 10(-3) s(-1) (mean +/- SD). Similar values were obtained from the dissociation kinetics measured after dilution of preformed factor VIII-vWF-RU1-Sepharose complexes. Identical rate constants were obtained for factor VIII binding to vWF from normal pooled plasma and to vWF from plasma of patients with hemophilia A. The kinetic parameters in this report allow estimation of the time needed for complex formation in vivo in healthy individuals and in patients with hemophilia A, in which monoclonally purified or recombinant factor VIII associates with endogenous vWF. Using the plasma concentration of vWF (50 nmol/L in monomers) and the obtained values for K(on) and K(off), the time needed to bind 50% of factor VIII is approximately 2 seconds.

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49

Vlot, AJ, SJ Koppelman, JC Meijers, C. Dama, HM van den Berg, BN Bouma, JJ Sixma, and GM Willems. "Kinetics of factor VIII-von Willebrand factor association." Blood 87, no. 5 (March 1, 1996): 1809–16. http://dx.doi.org/10.1182/blood.v87.5.1809.bloodjournal8751809.

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The binding of factor VIII to von Willebrand factor (vWF) is essential for the protection of factor VIII against proteolytic degradation in plasma. We have characterized the binding kinetics of human factor VIII with vWF using a centrifugation binding assay. Purified or plasma vWF was immobilized with a monoclonal antibody (MoAb RU1) covalently linked to Sepharose (Pharmacia LKB Biotechnology, Uppsala, Sweden). Factor VIII was incubated with vWF-RU1-Sepharose and unbound factor VIII was separated from bound factor VIII by centrifugation. The amount of bound factor VIII was determined from the decrease of factor VIII activity in the supernatant. Factor VIII binding to vWF-RU1-Sepharose conformed to the Langmuir model for independent binding sites with a Kd of 0.46 +/- 0.12 nmol/L, and a stoichiometry of 1.3 factor VIII molecules per vWF monomer at saturation, suggesting that each vWF subunit contains a binding site for factor VIII. Competition experiments were performed with a recombinant vWF (deltaA2-rvWF), lacking residues 730 to 910 which contain the epitope for MoAB RU1. DeltaA2-rvWF effectively displaced previously bound factor VIII, confirming that factor VIII binding to vWF-RU1-Sepharose was reversible. To determine the association rate constant (k(on)) and the dissociation rate constant (k(off)), factor VIII was incubated with vWF-RU1-Sepharose for various time intervals. The observed association kinetics conformed to a simple bimolecular association reaction with k(on) = 5.9 +/- 1.9 x 10(6) M(-1) s(-1) and k(off) = 1.6 +/- 1.2 x 10(-3) s(-1) (mean +/- SD). Similar values were obtained from the dissociation kinetics measured after dilution of preformed factor VIII-vWF-RU1-Sepharose complexes. Identical rate constants were obtained for factor VIII binding to vWF from normal pooled plasma and to vWF from plasma of patients with hemophilia A. The kinetic parameters in this report allow estimation of the time needed for complex formation in vivo in healthy individuals and in patients with hemophilia A, in which monoclonally purified or recombinant factor VIII associates with endogenous vWF. Using the plasma concentration of vWF (50 nmol/L in monomers) and the obtained values for K(on) and K(off), the time needed to bind 50% of factor VIII is approximately 2 seconds.

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50

Camacho, Carlos J., S. R. Kimura, Charles DeLisi, and Sandor Vajda. "Kinetics of Desolvation-Mediated Protein–Protein Binding." Biophysical Journal 78, no. 3 (March 2000): 1094–105. http://dx.doi.org/10.1016/s0006-3495(00)76668-9.

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