Identification of Cryptic Binding Sites Using MixMD with Standard and Accelerated Molecular Dynamics.

ABSTRACT: Protein dynamics play an important role in small molecule binding and can pose a significant challenge in the identification of potential binding sites. Cryptic binding sites have been defined as sites which require significant rearrangement of the protein structure to become physically accessible to a ligand. Mixed-solvent MD (MixMD) is a computational protocol which maps the surface of the protein using molecular dynamics (MD) of the unbound protein solvated in a 5% box of probe molecules with explicit water. This method has successfully identified known active and allosteric sites which did not require reorganization. In this study, we apply the MixMD protocol to identify known cryptic sites of 12 proteins characterized by a wide range of conformational changes. Of these 12 proteins, th

SUBMITTER: Smith RD 

PROVIDER: S-EPMC8091066 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature