[Coloquio BIFI] Modelling ligand-protein interaction

Published on 2012-07-04 17:30 CEST

Speaker: Claudio N. Cavasotto (School of Biomedical Informatics, University of Texas
Health Science Center at Houston
School of Biomedical Engineering, University of Texas at Austin)

Date & location: Thursday 18th November 2010, 12:30 (CET). Sala de grados del Edificio I+D, Campus Río Ebro

Computer-based simulations of biomolecular systems are playing an increasingly important role in structural biology and drug lead discovery. In silico modelling of ligand-protein interactions is an invaluable aid for the determination of molecular recognition patterns and a key component in structure-based drug design. I will first present the ligand-steered modeling method, where prediction of the interaction of known ligands with the protein is used to shape and optimize the binding site through a stochastic energy minimization, and with the final goal of using the modelled structures in highthroughput docking. Model quality and performance in docking and selectivity have been assessed for experimentally solved GPCRs. In the second part, I will present recent advances in biomolecular simulation concerning the use of quantum mechanical (QM) methods as an alternative to classical mechanics-based force-fields. A QM approach is especially attractive since de facto incorporates charge polarization and transfer effects, usually omitted in traditional force-fields. As a case study, the QM calculation of absolute and relative binding free energy of tetra-phosphopeptides to the SH2 domain of human LCK will be presented and compared to the failure of classical methods. The use of QM methods to estimate protein-water charge transfer will be also mentioned.

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