Computing the binding affinity of a ligand buried deep inside a protein with the hybrid steered molecular dynamics.

ABSTRACT: Computing the ligand-protein binding affinity (or the Gibbs free energy) with chemical accuracy has long been a challenge for which many methods/approaches have been developed and refined with various successful applications. False positives and, even more harmful, false negatives have been and still are a common occurrence in practical applications. Inevitable in all approaches are the errors in the force field parameters we obtain from quantum mechanical computation and/or empirical fittings for the intra- and inter-molecular interactions. These errors propagate to the final results of the computed binding affinities even if we were able to perfectly implement the statistical mechanics of all the processes relevant to a given problem. And they are actually amplified to various degrees ev

SUBMITTER: Villarreal OD 

PROVIDER: S-EPMC5253313 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature