Albert C Pan, David W Borhani, Ron O Dror, David E Shaw
DE Shaw Research, New York, NY 10036, USA. Albert.Pan@DEShawResearch.com
Drug discovery today 2013 JulIt is increasingly appreciated that the rates at which drugs associate with and dissociate from receptors--the binding kinetics--directly impact drug efficacy and safety. The molecular determinants of drug-receptor binding kinetics remain poorly understood, however, especially when compared with the well-known factors that affect binding affinity. The rational modulation of kinetics during lead optimization thus remains challenging. We review some of the key factors thought to control drug-receptor binding kinetics at the molecular level--molecular size, conformational fluctuations, electrostatic interactions and hydrophobic effects--and discuss several possible approaches for the rational design of drugs with desired binding kinetics. Copyright © 2013 Elsevier Ltd. All rights reserved.
Albert C Pan, David W Borhani, Ron O Dror, David E Shaw. Molecular determinants of drug-receptor binding kinetics. Drug discovery today. 2013 Jul;18(13-14):667-73
PMID: 23454741
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