Francesco Gervasio

Professor of Chemistry and Structural and Molecular Biology

Based at UCL

Personal Website

Biomolecular Simulations and Protein Dynamics

Our research focuses on the development of computational methods to study the dynamics of biomolecules.

We contributed to the development of a number of widely used simulation techniques and enhanced sampling algorithms: Metadynamics, Multiple Walkers, Parallel Tempering Metadynamics and Metadynamics-Transition Interface Sampling. We apply these methods to study large-scale conformational transitions in proteins and DNA, ligand binding, protein folding and ion translocation through membrane proteins. We also perform NMR and biophysical experiments to validate the results of our computations.

Recent highlights of our research was the development of an effective method to find hidden "cryptic" pockets in protein targets of biomedical interest; the clarification of the complex mode of action of the first allosteric inhibitor (SSR) of the Fibroblast Growth Factor Receptor. The free energy simulations have shown that SSR induces a previously unknown conformational change in the extracellular portion of FGFR. The accurate structural information obtained from the simulations has been used to design SSR derivatives now in pre-clinical development as anti-cancer agents. Furthermore, we combined co-evolutionary contacts and a novel coarse grain model to predict both the structure and the dynamics of proteins using only their primary sequence.

Selected publications

Molecular mechanism of SSR128129E, an extracellularly acting small molecule allosteric inhibitor of FGF receptor signaling
Herbert, C., Gervasio, F. L. et al
Cancer Cell (2013) 23 (4):489-501 
From residue co-evolution to protein conformational ensembles and functional dynamics
Sutto, L., Marsili, S., Valencia, A., Gervasio, F. L.
PNAS (2015) 112 (44):13567-13572
Understanding cryptic pocket formation in protein targets by enhanced sampling simulations
Oleinikovas, V., Saladino, G., Cossins, B. P., Gervasio, F. L.
Journal of the American Chemical Society (2016) 138 (43):14257-14263