DHFR Mutants Modulate Their Synchronized Dynamics with the Substrate by Shifting Hydrogen Bond Occupancies.

ABSTRACT: Antibiotic resistance is a global health problem in which mutations occurring in functional proteins render drugs ineffective. The working mechanisms of the arising mutants are seldom apparent; a methodology to decipher these mechanisms systematically would render devising therapies to control the arising mutational pathways possible. Here we utilize C_α-C_β bond vector relaxations obtained from moderate length MD trajectories to determine conduits for functionality of the resistance conferring mutants of Escherichia coli dihydrofolate reductase. We find that the whole enzyme is synchronized to the motions of the substrate, irrespective of the mutation introducing gain-of-function or loss-of function. The total coordination of the motions suggests changes in the

SUBMITTER: Cetin E 

PROVIDER: S-EPMC9795552 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature