Curry, S.H.: Plasma protein binding of chlorpromazine. Journal of Pharmacy and Pharmacology 22: 193–197 (1970). ArticlePubMedCASGoogle Scholar Dayton, P.G.; Israili, Z.H. and Perel, J.M.: Influence of binding on drug metabolism and distribution. Annals of New York Academy of Science ...
The computational modeling of ligand–protein binding thermodynamics is reviewed from the perspective of drug discovery. Methods for estimating the binding free energy and its components are presented in a hierarchy of decreasing complexity and computational requirement. Potentially accurate molecular dynamics...
normal mode analysis and molecular dynamics simulation CITY UNIVERSITY OF NEW YORK Lei Xie ChiuSee HongOne of the unaddressed challenges in drug discovery is that drug potency measured by protein-ligand binding affinity, such as ICand Kin vitro, is not correlated with drug activity in vivo. ...
14 May 2015 Published: 23 June 2015 Kinetics of protein-ligand unbinding via smoothed potential molecular dynamics simulations Luca Mollica1,*, Sergio Decherchi2,3,*, Syeda Rehana Zia2, Roberto Gaspari2, Andrea Cavalli1,4 & Walter Rocchia2 Drug discovery is expensive and high...
Computational Predictions of Drug-Protein Binding Kinetics with a Hybrid Molecular Dynamics, Brownian Dynamics, and Milestoning Approachdoi:10.1016/j.bpj.2018.11.3020Jagger, Benjamin R.Lee, Christopher T.McCammon, J. AndrewAmaro, Rommie E.
The compounds appear to compete for plasma protein binding sites as well as for binding sites on intrahepatic proteins. The biliary excretion data apparently fit the "ligand exclusion" model in which iopanoic acid acts as an inhibitor and competes with iodoxamic acid for binding to either of ...
Here we consider the theoretical principles of protein-ligand binding, molecular determinants, which control the drug-receptor binding kinetics. Understanding the molecular features underlying the receptor-protein binding kinetics will contribute to the rational design of drugs with desired properties....
Structure-based drug design has often been restricted by the rather static picture of protein–ligand complexes presented by crystal structures, despite the widely accepted importance of protein flexibility in biomolecular recognition. Here we report a detailed experimental and computational study of the ...
Consequently, we suggest a kinetic-driven selectivity gate between canonical and secondary coupling which arises from differential favourability of G protein binding to the agonist-bound receptor active state. The authors show G protein subtype selectivity at the β1-adrenergic receptor is driven by ...
The potential influence of protein binding kinetics on elimination from liver sinusoids was evaluated by means of a “well-stirred” model (I) and a “tube” model (II). When the dissociation rate constant (k−1) is at the estimated maximum, equilibrium is maintained during the passage of...