The dissociation rate (k off) associated with ligand unbinding events from proteins is a
parameter of fundamental importance in drug design. Here we review recent major …

Introduction Drug–target thermodynamic and kinetic information have perennially important
roles in drug design. The prediction of protein–ligand unbinding, which can provide …

Biomolecular binding kinetics including the association (k on) and dissociation (k off) rates
are critical parameters for therapeutic design of small-molecule drugs, peptides, and …

It is widely accepted that drug–target association and dissociation rates directly affect drug
efficacy and safety. To rationally optimize drug binding kinetics, one must know the atomic …

One of the unaddressed challenges in drug discovery is that drug potency determined in
vitro is not a reliable indicator of drug activity in vivo. Accumulated evidence suggests that in …

The determination of drug residence times, which define the time an inhibitor is in complex
with its target, is a fundamental part of the drug discovery process. Synthesis and …

The prediction of drug–target binding and unbinding kinetics that occur on time scales
between milliseconds and several hours is a prime challenge for biased molecular …

The recent paradigm shift toward the use of the kinetics parameters in place of
thermodynamic constants is leading the computational chemistry community to develop …

Interest in ligand binding kinetics has been growing rapidly, as it is being discovered in more
and more systems that ligand residence time is the crucial factor governing drug efficacy …

Drug discovery is expensive and high-risk. Its main reasons of failure are lack of efficacy and
toxicity of a drug candidate. Binding affinity for the biological target has been usually …