The displacement of water molecules from the active site upon the binding of a ligand has a significant impact on the binding free energy though it is generally treated simplistically in virtual screening applications. We incorporated solvation thermodynamic maps generated using a grid-based implementation of inhomogeneous fluid solvation theory (GIST) into the docking program DOCK 3.7, optimized the method retrospectively against the DUD-E database of useful decoys and prospectively tested binding predictions to cytochrome c-peroxidase with compounds screened from a purchasable compound database. The results showed moderate improvements in retrospective tests though very good results in prospective tests. We will discuss the methodology, results, and future challenges to better including solvation into virtual screening.

Incorporating solvation thermodynamic mapping into docking

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.