How to deal with multiple binding poses in alchemical relative protein-ligand binding free energy calculations.

ABSTRACT: Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enh

SUBMITTER: Kaus JW 

PROVIDER: S-EPMC4462751 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature