A computational study of the Factor V Leiden mutation and its effect on blood coagulation

Isabelle M. Zagarri
Dr. Bill R. Miller (A.T. Still University) and Dr. Andrew Kauffmann, Faculty Mentors

Factor V (FV) is a critical blood-clotting protein of the coagulation system. This inactive form circulates the blood stream until needed, then is activated to Factor Va (FVa) by thrombin. FVa can be deactivated by a complex of activated protein C and protein S (APC:PS), inhibiting the coagulation cascade. A single amino acid mutation from an arginine to a glutamine at residue 506 causes Factor V Leiden (FVL), which impairs the binding of APC:PS to FVa, increasing the likelihood of abnormal blood clots. There is no cure for this mutation – only anticoagulant drugs are prescribed. 

Using computational methods, we observe binding interactions between FVa and APC. Results show that the Leiden mutant forms a less stable complex with APC than it does with the wild type. Future work includes simulating and analyzing FVa:APC:PS and FVL:APC:PS, and determining the important amino acid binding sites.

Keywords: Factor V Leiden, anticoagulant, computational chemistry, drug discovery, molecular dynamics, molecular docking, coagulation system, Factor Va

Topic(s):Biochemistry and Molecular Biology
Chemistry
Biology

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA