Umbrella Sampling Simulations Measure Switch Peptide Binding and Hydrophobic Patch Opening Free Energies in Cardiac Troponin.

ABSTRACT: The cardiac troponin (cTn) complex is an important regulatory protein in heart contraction. Upon binding of Ca²⁺, cTn undergoes a conformational shift that allows the troponin I switch peptide (cTnI_SP) to be released from the actin filament and bind to the troponin C hydrophobic patch (cTnC_HP). Mutations and modifications to this complex can change its sensitivity to Ca²⁺ and alter the energetics of the transition from the Ca²⁺-unbound, cTnI_SP-unbound form to the Ca²⁺-bound, cTnI_SP-bound form. We utilized targeted molecular dynamics (TMD) to obtain a trajectory of this transition pathway, followed by umbrella sampling to estimate the free energy associated with the cTnI_SP-cTnC_HP bi

SUBMITTER: Cool AM 

PROVIDER: S-EPMC9712266 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature