Computational Exploration and Characterization of Potential Calcium Sensitizing Mutations in Cardiac Troponin C.

ABSTRACT: Calcium-dependent heart muscle contraction is regulated by the cardiac troponin protein complex (cTn) and specifically by the N-terminal domain of its calcium binding subunit (cNTnC). cNTnC contains one calcium binding site (site II), and altered calcium binding in this site has been studied for decades. It has been previously shown that cNTnC mutants, which increase calcium sensitization may have therapeutic benefits, such as restoring cardiac muscle contractility and functionality post-myocardial infarction events. Here, we computationally characterized eight mutations for their potential effects on calcium binding affinity in site II of cNTnC. We utilized two distinct methods to estimate calcium binding: adaptive steered molecular dynamics (ASMD) and thermodynamic integration (TI). We o

SUBMITTER: Hantz ER 

PROVIDER: S-EPMC10497304 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature