Resolving the problem of trapped water in binding cavities: prediction of host-guest binding free energies in the SAMPL5 challenge by funnel metadynamics.

ABSTRACT: The funnel metadynamics method enables rigorous calculation of the potential of mean force along an arbitrary binding path and thereby evaluation of the absolute binding free energy. A problem of such physical paths is that the mechanism characterizing the binding process is not always obvious. In particular, it might involve reorganization of the solvent in the binding site, which is not easily captured with a few geometrically defined collective variables that can be used for biasing. In this paper, we propose and test a simple method to resolve this trapped-water problem by dividing the process into an artificial host-desolvation step and an actual binding step. We show that, under certain circumstances, the contribution from the desolvation step can be calculated without introducing fu

SUBMITTER: Bhakat S 

PROVIDER: S-EPMC5239820 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature