Molecular Dynamics Simulations of the Cardiac Ryanodine Receptor Type 2 (RyR2) Gating Mechanism.

ABSTRACT: Mutations in the cardiac ryanodine receptor type 2 (RyR2) have been linked to fatal cardiac arrhythmias such as catecholaminergic polymorphic ventricular tachycardia (CPVT). While many CPVT mutations are associated with an increase in Ca²⁺ leak from the sarcoplasmic reticulum, the mechanistic details of RyR2 channel gating are not well understood, and this poses a barrier in the development of new pharmacological treatments. To address this, we explore the gating mechanism of the RyR2 using molecular dynamics (MD) simulations. We test the effect of changing the conformation of certain structural elements by constructing chimera RyR2 structures that are derived from the currently available closed and open cryo-electron microscopy (cryo-EM) structures, and we then use MD simulatio

SUBMITTER: Greene D 

PROVIDER: S-EPMC9720719 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature