Using Computational Methods to Analyze Structural Changes in the Factor V Leiden Mutation to Determine Specific Binding Interactions and Stability

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. The active form of FV is Factor Va (FVa), which can be deactivated by the activated protein C (APC) and protein S (PS) complex (APC:PS). A single amino acid mutation, R506Q, a critical APC:PS binding site, causes Factor V Leiden (FVL) which increases the likelihood of abnormal blood clots. There is currently no cure for this mutation – only anticoagulant drugs are prescribed. Thus, we study the binding site of FVa and APC:PS to further investigate this mutation and potentially develop a specific treatment. Using computational methods such as molecular docking and molecular dynamics, we evaluate the stability of the apo structures then observe the interactions between FVa and APC:PS. We will compare these interactions with FVL and APC:PS to analyze the differences to further understand the role of APC:PS in deactivation of blood clotting functions.

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: Poster Presentation

Session: TBA
Location: TBA
Time: TBA