Comprehensive Approach to Simulating Large Scale Conformational Changes in Biological Systems Utilizing a Path Collective Variable and New Barrier Restraint.

ABSTRACT: Conformational sampling of complex biomolecules is an emerging frontier in drug discovery. Advances in lab-based structural biology and related computational approaches like AlphaFold have made great strides in obtaining static protein structures for biologically relevant targets. However, biology is in constant motion, and many important biological processes rely on conformationally driven events. Conventional molecular dynamics (MD) simulations run on standard hardware are impractical for many drug design projects, where conformationally driven biological events can take microseconds to milliseconds or longer. An alternative approach is to focus the search on a limited region of conformational space defined by a putative reaction coordinate (i.e., path collective variable). The search sp

SUBMITTER: Kolossvary I 

PROVIDER: S-EPMC10278137 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature