Binding pocket dynamics along the recovery stroke of human β-cardiac myosin.

ABSTRACT: The druggability of small-molecule binding sites can be significantly affected by protein motions and conformational changes. Ligand binding, protein dynamics and protein function have been shown to be closely interconnected in myosins. The breakthrough discovery of omecamtiv mecarbil (OM) has led to an increased interest in small molecules that can target myosin and modulate its function for therapeutic purposes (myosin modulators). In this work, we use a combination of computational methods, including steered molecular dynamics, umbrella sampling and binding pocket tracking tools, to follow the evolution of the OM binding site during the recovery stroke transition of human β-cardiac myosin. We found that steering two internal coordinates of the motor domain can recapture the main feature

SUBMITTER: Akter F 

PROVIDER: S-EPMC10231807 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature