Role of ATP Hydrolysis and Product Release in the Translocation Mechanism of SARS-CoV-2 NSP13.

ABSTRACT: In response to the emergence of COVID-19, caused by SARS-CoV-2, there has been a growing interest in understanding the functional mechanisms of the viral proteins to aid in the development of new therapeutics. Nonstructural protein 13 (nsp13) helicase is an attractive target for antivirals because it is essential for viral replication and has a low mutation rate, yet the structural mechanisms by which this enzyme binds and hydrolyzes ATP to cause unidirectional RNA translocation remain elusive. Using Gaussian accelerated molecular dynamics (GaMD), we generated comprehensive conformational ensembles of all substrate states along the ATP-dependent cycle. Shape-GMM clustering of the protein yields four protein conformations that describe an opening and closing of both the ATP pocket and the R

SUBMITTER: Lawal MM 

PROVIDER: S-EPMC11256563 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature