Adaptive Landscape Flattening Accelerates Sampling of Alchemical Space in Multisite λ Dynamics.

ABSTRACT: Multisite λ dynamics (MSλD) is a powerful emerging method in free energy calculation that allows prediction of relative free energies for a large set of compounds from very few simulations. Calculating free energy differences between substituents that constitute large volume or flexibility jumps in chemical space is difficult for free energy methods in general, and for MSλD in particular, due to large free energy barriers in alchemical space. This study demonstrates that a simple biasing potential can flatten these barriers and introduces an algorithm that determines system specific biasing potential coefficients. Two sources of error, deep traps at the end points and solvent disruption by hard-core potentials, are identified. Both scale with the size of the perturbed substituent and are r

SUBMITTER: Hayes RL 

PROVIDER: S-EPMC5824625 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature