In silico characterization of molecular interactions in biological systems

CAVASOTTO, CLAUDIO N.

Oro Verde, Entre Ríos

Congreso; 3er. Congreso Argentino de Bioinformática y Biología Computacional; 2012

Today,computational simulation is an invaluable tool to study macromolecularassociation, enzymatic reactions, and to understand at a molecular level therelationship between structure, dynamics and function.  Thus, it provides an efficient and insightfulcomplement to experimental evaluation. At the core of these calculations lies the potential energy function,which describes the intermolecular interactions in the system.  The the latest developments of our researchgroup will be presented, focusing on the application of in silico methodsto problems in the areas of structural biology, drug discovery, binding freeenergy calculation, and cheminformatics, namely:  i) the ligand-steered homology modellingmethod, where the interaction of known ligands with the receptor is used toshape and optimize the binding site through a stochastic global energyminimization, with the final goal of using the modelled structures instructure-based drug discovery; ii) the discovery of novel modulators of GPCRsand nuclear receptors through coarse-grained high-throughput docking followedby experimental evaluation; iii) the use of quantum mechanical (QM) methods tostudy biomacromolecular interaction; as a case study, the QM calculation ofabsolute and relative binding free energy of tetra-phosphopeptides to the SH2domain of human LCK will be presented and compared to the failure of classicalmethods.  Current limitations ofcomputational methods and future trends will be also discussed.