Program

I.4 -- Invited, IWTCP-3

Date: Monday, 27 July 2015

Time: 14h35 - 15h10

Improved prediction of protein complex binding affinities: the role of entropy

Antonio Trovato

Dipartimento di Fisica e Astronomia "G. Galilei", Universita di Padova and CNISM, Unita di Padova, Via Marzolo 8, 35131 Padova, Italy

Protein-protein interactions play an essential role in the biological function of many proteins. We will tackle the problem of predicting the binding affinities of protein complexes, based on the knowledge of both the complex and the unbound subunits. We will rely on the BACH statistical potential, recently developed in our group, that showed excellent performances in discriminating the native states of monomeric proteins. We will first show that the BACH scoring function is successful as well in recognizing native and close-to-native protein complexes. We will then employ our scoring function as the basis of a method to predict the binding affinities of protein complexes, which is in general a very difficult task. We will show that, in order to improve the predictive performance of our method, it is crucial to properly estimate how the change in protein fluctuations upon binding determines the entropic contribution to the binding affinity. This is done by means of simple coarse-grained elastic network models; yet, it relies on determining the proper structure-dependent elastic constant by means of a novel self-consistent procedure based on matching the residue mobilities computed within the network model with those estimated from molecular dynamics all atom explicit solvent simulations initiated from the experimental structures.

Presenter: Antonio Trovato