Exploring the Interaction of Some N- Benzyloxycarbonyl-L-Phenyl Alanyl-L-Alanine Ketones and Bovine Spleen Cathepsin B by Molecular Modeling and Binding Free Energy Calculation

Abstract

A semi-empirical method for estimation of binding free energy, recently proposed by Aqvist and coworkers, has been effectively tested in several protein-ligand binding cases. We have applied this linear interaction energy method to predict the binding of some N-benzy- loxycarbonyl-L-phenyl alanyl-L-alanine ketones with bovine cathepsin B and computed the respective absolute binding constants from averages of molecular dynamics simulations. It is found that the computer simulation results agree well with available experimental data and make it possible to understand better the origin of tight binding and inhibitor specificity of cathepsin B.