University of Cagliari
FACOLTA’ DI SCIENZE
DIPARTIMENTO DI FISICA
Giovedì 16 Settembre ore 15.00, Aula A presso il Dipartimento di Fisica - Cittadella Universitaria Monserrato
il Prof. Francesco Luigi Gervasio, head of Computational Biophysics, Spanish National Cancer Research Center, Madrid, Spain (flgervasio@cnio.es), terrà un seminario dal titolo:
"Combining Free Energy Methods and Experiments to Study Large-Scale Protein Dynamics"
Abstract
Protein plasticity represents both a challenge and an opportunity for computational biophysics. Exploring the conformational space of protein with sufficient detail is computationally very demanding and often beyond the reach even for state-of-the-art atomistic molecular simulations techniques. If it were possible, however, it could open the avenue to the design of more selective drug candidates. Here we show how methods developed to accelerate rare events can be used in combination with experiments to study large-scale conformational transitions and ligand binding.
Using GPU machines, new sampling methods [1], and NMR experiments, we determined the importance of a single amino-acid in ruling the dynamic equilibrium between active and inactive states of the oncogenic c-Src protein. A similar approach, mainly based on Metadynamics [2] was used to study the mode of inhibition of a COX-2 selective drug [3] and the very complex mode of action of an allosteric inhibitor of a receptor tyrosine kinase.
1. D. Branduardi, F. L. Gervasio and M. Parrinello. Rare events in molecular systems: From A to B in Free Energy Space J. Chem. Phys., 2007,126, 054103,
3. V. Limongelli, F.L. Gervasio et al. Proc. National Acad. Sci. USA, 2010, 107, 5411–5416.
Dipartimento di Fisica
Universita degli Studi di Cagliari & UOS SLACS, IOM/CNR
Cittadella Monserrato
09042 Monserrato-CA
+390706754933 (tel)
+39070510171 (fax)