Simulating Protein Mediated Hydrolysis of ATP and Other Nucleoside Triphosphates by Combining QM/MM Molecular Dynamics with Advances in Metadynamics.

ABSTRACT: The protein mediated hydrolysis of nucleoside triphosphates such as ATP or GTP is one of the most important and challenging biochemical reactions in nature. The chemical environment (water structure, catalytic metal, and amino acid residues) adjacent to the hydrolysis site contains hundreds of atoms, usually greatly limiting the amount of the free energy sampling that one can achieve from computationally demanding electronic structure calculations such as QM/MM simulations. Therefore, the combination of QM/MM molecular dynamics with the recently developed transition-tempered metadynamics (TTMetaD), an enhanced sampling method that can provide a high-quality free energy estimate at an early stage in a simulation, is an ideal approach to address the biomolecular nucleoside triphosphate hydro

SUBMITTER: Sun R 

PROVIDER: S-EPMC5425946 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature