Constant pH Replica Exchange Molecular Dynamics in Explicit Solvent Using Discrete Protonation States: Implementation, Testing, and Validation.

ABSTRACT: By utilizing Graphics Processing Units, we show that constant pH molecular dynamics simulations (CpHMD) run in Generalized Born (GB) implicit solvent for long time scales can yield poor pK_a predictions as a result of sampling unrealistic conformations. To address this shortcoming, we present a method for performing constant pH molecular dynamics simulations (CpHMD) in explicit solvent using a discrete protonation state model. The method involves standard molecular dynamics (MD) being propagated in explicit solvent followed by protonation state changes being attempted in GB implicit solvent at fixed intervals. Replica exchange along the pH-dimension (pH-REMD) helps to obtain acceptable titration behavior with the proposed method. We analyzed the effects of various paramete

SUBMITTER: Swails JM 

PROVIDER: S-EPMC3985686 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature