Research

My research focuses on studying the structure and dynamics of proteins involved in the blood coagulation cascade in order to explain their function at atomic level of detail. One aspect of my research is understanding how oxidative stress present during inflammation alters the function, stability and binding behavior of blood coagulation factors. In particular, I study the function of von Willebrand Factor, which is essential in slowing down platelets in case of arterial injury and the self-association properties of fibrinogen, which is important to stabilize the blood clot. The main technique that I use is molecular dynamics simulations often combined with accelerated sampling methods or free energy perturbation. Since I believe that it is essential to validate computational results through experiments, I also study the behavior of von Willebrand Factor through a flow chamber assay which mimics the shear forces present in flowing blood. Oxidative stress due to traumatic injury is thought to increase the thrombotic activity of blood coagulation factors.

Biochemically, oxidation leads to the conversion of methionine residues to methionine sulfoxide. My research aims at understanding how this conversion affects the structure and function of key coagulation factors explaining their increased thrombotic activity. Insights gained onto the structural mechanism of coagulation factors can help structure based drug design to find therapeutics that can treat thrombotic diseases without causing life threatening bleeding.

Pathological blood clots can often be caused by biomedical devices implanted in the body. For this reason, I am interested in studying the interaction between proteins and material surfaces using a combination of Monte Carlo and molecular dynamics simulations. Other side projects include studying the allosteric regulation and binding properties of adhesive proteins present in bacterial fimbria.