Free Energy Simulations of Receptor-Binding Domain Opening of the SARS-CoV-2 Spike Indicate a Barrierless Transition with Slow Conformational Motions.

ABSTRACT: Infection by sarbecoviruses begins with the attachment of the homotrimeric viral "spike" protein to the angiotensin-converting enzyme 2 receptor on the surface of mammalian cells. This requires one or more receptor-binding domains (RBDs) to be in the open (up) position. Here, we present the results of long molecular dynamics simulations with umbrella sampling (US) to compute a one-dimensional free energy profile of RBD opening/closing and the associated transition times. After ≃3.58μs of simulation time per US window (∼229 μs in total), which was required to approach trajectory decorrelation, the computed free energy profile was found to be without large barriers. This suggests that the RBD diffuses between the open and closed positions without significant energetic hindrance. This

SUBMITTER: Ovchinnikov V 

PROVIDER: S-EPMC10578350 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature