Integrating comparative modeling and accelerated simulations reveals conformational and energetic basis of actomyosin force generation.

ABSTRACT: Muscle contraction is performed by arrays of contractile proteins in the sarcomere. Serious heart diseases, such as cardiomyopathy, can often be results of mutations in myosin and actin. Direct characterization of how small changes in the myosin-actin complex impact its force production remains challenging. Molecular dynamics (MD) simulations, although capable of studying protein structure-function relationships, are limited owing to the slow timescale of the myosin cycle as well as a lack of various intermediate structures for the actomyosin complex. Here, employing comparative modeling and enhanced sampling MD simulations, we show how the human cardiac myosin generates force during the mechanochemical cycle. Initial conformational ensembles for different myosin-actin states are learned f

SUBMITTER: Ma W 

PROVIDER: S-EPMC9992861 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature