Conformational Changes and ATP Hydrolysis in Zika Helicase: The Molecular Basis of a Biomolecular Motor Unveiled by Multiscale Simulations.

ABSTRACT: We computationally study the Zika NS3 helicase, a biological motor, using ATP hydrolysis energy for nucleic acid remodeling. Through molecular mechanics and hybrid quantum mechanics/molecular mechanics simulations, we explore the conformational landscape of motif V, a conserved loop connecting the active sites for ATP hydrolysis and nucleic acid binding. ATP hydrolysis, initiated by a meta-phosphate group formation, involves the nucleophilic attack of a water molecule activated by Glu286 proton abstraction. Motif V hydrogen bonds to this water via the Gly415 backbone NH group, assisting hydrolysis. Posthydrolysis, free energy is released when the inorganic phosphate moves away from the coordination shell of the magnesium ion, inducing a significant shift in the conformational landscape of

SUBMITTER: Garcia-Martinez A 

PROVIDER: S-EPMC10852352 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature