The transmission of mutation effects in a multiprotein machine: A comprehensive metadynamics study of the cardiac thin filament.

ABSTRACT: The binding of Ca²⁺ ions within the troponin core of the cardiac thin filament (CTF) regulates normal contraction and relaxation. Mutations within the troponin complexes are known to alter normal functions and result in the eventual development of cardiomyopathy. However, despite the importance of the problem, detailed microscopic knowledge of the mechanism of pathogenic effect of point mutations and their effects on the conformational free energy surface of CTF remains elusive. Mutations are known to transmit their effects hundreds of angstroms along this protein complex and between different component proteins. To explore the impact of point mutations on the conformational free energy barrier between the closed and blocked state of CTF, and to understand the transmission of mu

SUBMITTER: Ghanta KP 

PROVIDER: S-EPMC11568392 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature