Computational Tools for Structure Based Drug Design

This paper presents some methods found to be of utility in Structure Based Drug Design. We describe the use of combined molecular mechanics, small molecule conformational search and continuum solvation models to develop semi-quantitative ranking of relative binding free energy for small molecules to proteins. We present results of these types of calculations for several proteins: thymidylate synthase, FK506 binding protein (FKBP), and stromelysin-1 (MMP-3).