Dynamics of the Pre-Powerstroke Myosin Lever Arm and the Effects of Omecamtiv Mecarbil.

ABSTRACT: The binding of small molecules to sarcomeric myosin can elicit powerful effects on the chemomechanical cycle, making them effective therapeutics in the clinic and research tools at the benchtop. However, these myotropes can have complex effects that act on different phases of the crossbridge cycle and which depend on structural, dynamic, and environmental variables. While small molecule binding sites have been identified crystallographically and their effects on contraction studied extensively, small molecule-induced dynamic changes that link structure-function are less studied. Here, we use molecular dynamics simulations to explore how omecamtiv mecarbil (OM), a cardiac myosin-specific myotrope, alters the coordinated dynamics of the lever arm and the motor domain in the pre-powerstroke s

SUBMITTER: Childers MC 

PROVIDER: S-EPMC11477208 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature