Article
Drug Design for Protein Kinases and Phosphatases: Flexible-Receptor Docking, Binding Affinity and Specificity, and Drug-Binding Kinetics
Current Pharmaceutical Design
(2013)
Abstract
This article reviews some of our experiences on applying computational techniques to aid the design of drugs targeting protein kinases and phosphatases. It is not a comprehensive review. Rather, it focuses on several less explored approaches or ideas that we have experiences on. It reviews some recent improvements on the Poisson-Boltzmann/Surface Area model for calculating binding affinity and discusses ways to perform calculations that are more tolerant to statistical and systematic errors. Several new ways to incorporate protein flexibility in molecular docking and estimating binding affinity are also discussed. Its discussions also go beyond binding affinity to considering drug-binding kinetics, not only on investigating protein-ligand interactions in isolation, but also on accounting for upstream and downstream influences that can occur in cells, through kinetic modeling of cell signaling. This review also describes a quick molecular simulation method for understanding drug-binding kinetics at the molecular level, with the hope of generating guiding principles for designing drugs with the desired kinetic properties. Sources of drug-binding selectivity that appear obvious but often overlooked are also discussed.
Disciplines
Publication Date
June 1, 2013
DOI
10.2174/1381612811319260006
Citation Information
Chung Wong and Sneha Bairy. "Drug Design for Protein Kinases and Phosphatases: Flexible-Receptor Docking, Binding Affinity and Specificity, and Drug-Binding Kinetics" Current Pharmaceutical Design Vol. 19 Iss. 26 (2013) p. 4739 - 4754 Available at: http://works.bepress.com/chung-wong/10/