Thursday, 26th June, 2014, 11.00-12.00

Modelling protein dynamics

Proteins are molecules involved in essentially all the complex biochemical reactions that take place in living organisms. In order to perform their functions they undergo conformational fluctuations on timescales ranging from nanoseconds to milliseconds and beyond. It is, therefore, important to develop methods capable of characterizing these motions. Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique that enables the determination of the structures and dynamics of proteins at atomic resolution. Since NMR measurements produce values of observables resulting from time and ensemble averages, their interpretation is facilitated by considering ensembles of structures. The determination of an ensemble of conformations from experimental information about just average values is seem to be an ill-defined problem. In the seminar I will show that by using the Principle of Maximum Entropy (PME) it is possible to chose a special distribution (i.e., an ensemble of structures) among all those that are consistent with the experimentally-determined average values by imposing the average values themselves as thermodynamic constraints. This particular maximum entropy distribution provides an accurate representation of the unknown Boltzmann distribution of the system. The problem of determining structural ensembles can thus be solved unambiguously without making any additional assumption apart from the requirement that the experimental data should be consistent with it in the sense of the maximum entropy principle. To implement the maximum entropy principle in a computationally efficient manner, as we demonstrate in this paper in the case of NOE data, it is possible to use experimental measurements as replica-averaged structural restraints in molecular dynamics simulations.

Speaker: Andrea Cavalli, Institute for Research in Biomedicine, Department of Chemistry, University of Cambridge.

Room Xipre (seminar 173.06), PRBB.