Methods of exploring protein–ligand interactions to guide medicinal chemistry efforts

Abstract

We present a number of techniques to analyze protein–ligand interactions in the context of medicinal chemistry: crystal Contract Preferences, Electrostatic Maps and pharmacophore screening using Hückel Theory. Contact Preferences is a statistical technique to predict hydrophobic and hydrophilic geometry in receptor active sites. Electrostatic Maps use the Poisson-Boltzmann Equation to model solvation effects and are particularly useful for predicting hydrophobic regions. Pharmacophore annotation with Hückel Theory provides finer detail of hydrogen bonding interactions, including CH.O interactions. Applications to AblK:Gleevec and CDK2 virtual screening are presented.