Unraveling Mutation-Induced Protein Communication Pathways in the Actomyosin Complex: Insights from Comprehensive Metadynamics Simulations.

ABSTRACT: The binding of myosin to the actin filament in the cardiac thin filament (CTF) plays a critical role in regulating normal contraction and relaxation. Hereditary mutations in human β-cardiac myosin can result in severe manifestations of heart failure. However, despite its significance, how these mutations create contractile dysfunction and eventually drive pathogenic heart remodeling remains unknown. The effect of mutations on the conformational free energy barriers between different states of the actomyosin complex remains elusive. Mutations can transmit effects across many angstroms in protein complexes, affecting multiple associated proteins and thereby altering function. To investigate the effect of point mutations in myosin on the free energy barriers of ADP release and the conformatio

SUBMITTER: Ghanta KP 

PROVIDER: S-EPMC12398948 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature