Molecular determinants of drug–receptor binding kinetics

Albert C. Pan, David W. Borhani, Ron O. Dror, David E. Shaw
2013 Drug Discovery Today  
It is increasingly appreciated that the rates at which drugs associate with and dissociate from receptorsthe binding kinetics -directly impact drug efficacy and safety. The molecular determinants of drugreceptor binding kinetics remain poorly understood, however, especially when compared with the wellknown 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
more » ... 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.
doi:10.1016/j.drudis.2013.02.007 pmid:23454741 fatcat:iqta53cmabaztbnhfvithz3jye