Computational Analysis of Factor V Leiden: APC and Protein S Interactions

Audrey Brown
Dr. Bill R. Miller (A.T. Still University) and Dr. Andrew Kauffmann, Faculty Mentors

Factor V (FV) is a key regulatory protein in the coagulation cascade. FV remains inactive until thrombin converts it into active Factor Va (FVa). Under normal conditions, clotting is regulated by the activated protein C and protein S (APC:PS) complex, which inactivates FVa. However, in Factor V Leiden (FVL), a single point mutation disrupts the APC:PS deactivation and increases the risk of abnormal clotting. Currently, no specific cure exists for FVL. 
Molecular modeling was performed to characterize the stability of APC and PS, as well as the specific binding interactions within the APC:PS complex. Molecular dynamics simulations (1000 ns, triplicate) and analysis for stability and conformational dynamics of APC, PS, and the APC:PS complex. Preliminary results indicate favorable binding of APC:PS, supporting their integral role in FVa regulation. These results provide insight into how the APC:PS complex deactivates blood clotting.

 

Keywords: Factor V Leiden, anticoagulant, computational chemistry , drug discovery, molecular dynamics, Activated Protein C , Protein S, coagulation system

Topic(s):Biochemistry and Molecular Biology
Chemistry
Biology

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA