Site-Specific Fragment Identification Guided by Single-Step Free Energy Perturbation Calculations.

ABSTRACT: The in-silico Site Identification by Ligand Competitive Saturation (SILCS) approach identifies the binding sites of representative chemical entities on the entire protein surface, information that can be applied for computational fragment-based drug design. In this study, we report an efficient computational protocol that uses sampling of the protein-fragment conformational space obtained from the SILCS simulations and performs single step free energy perturbation (SSFEP) calculations to identify site-specific favorable chemical modifications of benzene involving substitutions of ring hydrogens with individual non-hydrogen atoms. The SSFEP method is able to capture the experimental trends in relative hydration free energies of benzene analogues and for two datasets of experimental relative

SUBMITTER: Raman EP 

PROVIDER: S-EPMC3490637 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature