Molecular dynamics simulations of Factor Xa: insight into conformational transition of its binding subsites.
Protein flexibility and conformational diversity is well known to be a key characteristic of the function of many proteins. Human blood coagulation proteins have multiple substrates, and various protein-protein interactions are required for the smooth functioning of the coagulation cascade to maintain blood hemostasis. To address how a protein may cope with multiple interactions with its structurally diverse substrates and the accompanied structural changes that may drive these changes, we studied human Factor X. We employed 20 ns of molecular dynamics (MD) and steered molecular dynamics (SMD) simulations on two different conformational forms of Factor X, open and closed, and observed an interchangeable conformational transition from one to another. This work also demonstrates the roles of various aromatic residues involved in aromatic-aromatic interactions, which make this dynamic transition possible.
Singh
Narender
N
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5001, USA.
Briggs
James M
JM
D001665:Binding Sites; D003461:Crystallography; D005167:Factor VII / Q000737:chemistry / Q000378:metabolism; D015951:Factor Xa / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011516:Prothrombin / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D009842:Oligopeptides; D005167:Factor VII; D011516:Prothrombin; D015951:Factor Xa