Introduction on kinetics
Quest for new drug discovery usually involves a clear understanding of ligand binding to its receptor. Free binding energy helps to rank compounds and allows to select those based on their target affinity. Drug discovery programs focused on optimization of target affinity as a proxy of in-vivo efficacy. Within the last years, researchers have increasingly become interested in measuring and understanding drugs’ binding kinetics. Namely, the time in which drug and its target associate and dissociate.
Until recently, few methods offered the possibility to determine kinetics parameters and almost none at atomistic resolution. Amazing recent emergence of computational methods provided powerful tools in measuring and understanding binding event. It offers interesting and accurate methods to determine qualitative (binding mode) and quantitative (binding energy, Kon, Koff) parameters in a single atomistic approach.
Determination of these parameters with HTMD has been reviewed in previous posts:
such as this one . Recent works that highlight the importance of binding, molecular recognition and molecular determinants for rational optimization have been reviewed here.
Reference: Noelia Ferruz, and Gianni De Fabritiis Binding Kinetics in Drug Design Mol. Inf. 2016, doi: 10.1002/minf.201501018