Polymorph sampling with coupling to extended variables: enhanced sampling of polymorph energy landscapes and free energy perturbation of polymorph ensembles.

ABSTRACT: A novel approach to computationally enhance the sampling of molecular crystal structures is proposed and tested. This method is based on the use of extended variables coupled to a Monte Carlo based crystal polymorph generator. Inspired by the established technique of quasi-random sampling of polymorphs using the rigid molecule constraint, this approach represents molecular clusters as extended variables within a thermal reservoir. Polymorph unit-cell variables are generated using pseudo-random sampling. Within this framework, a harmonic coupling between the extended variables and polymorph configurations is established. The extended variables remain fixed during the inner loop dedicated to polymorph sampling, enforcing a stepwise propagation of the extended variables to maintain system exp

SUBMITTER: Chan EJ 

PROVIDER: S-EPMC11789163 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature