An interdisciplinary approach to model the binding of flexible proteins: Applications to coagulation Factor VIII and the von Willebrand Factor.

D. Flemming Hansen (primary)
Structural and Molecular Biology
University College London
Adrian Shepherd (secondary)
Biological Sciences


Dynamics of proteins plays critical roles for functions and interactions. Traditional structural biology provides limited insights on highly flexible, yet functional, regions, since these are absent in most crystal- and cryo-EM structures. This project will utilize an approach that combines molecular biology, NMR spectroscopy, and molecular dynamics simulations to characterise how dynamic proteins interact with binding partners. Focus will be on two blood coagulation factors: von Willebrand factor and factor VIII, where the disordered a3 domain of factor VIII is imperative for high-affinity binding. This project is highly interdisciplinary, involving substantial elements of computational modelling, NMR spectroscopy and wet-lab work.


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2 N. Shiltagh, J. Kirkpatrick, L.D. Cabrita, T.A.J. Mckinnon, K. Thalassinos, E.G.D. Tuddenham, and D.F. Hansen. “Solution structure of the major factor VIII binding region on von Willebrand factor.” Blood 123, (2014): 4143-4151.
3 A. Kuzmanic, R.B. Pritchard, D.F. Hansen, F.L. Gervasio, J. Phys. Chem. Lett. 10, (2019): 1928-1934
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5 A. Yee, A.N. Oleskie, A.M. Dosey, C.A. Kretz, R.D. Gildersleeve, S. Dutta, M. Su, D. Ginsburg, and G. Skiniotis.. “Visualization of an N-terminal fragment of von Willebrand factor in complex with factor VIII”. Blood. 126, (2015): 939–42

Molecules, cells and industrial biotechnology
Area of Biology
BiotechnologyStructural Biology
Techniques & Approaches
BiochemistryBiophysicsMathematics / StatisticsMolecular BiologySimulation / Modelling