Validation of Novel in silico Methodologies

GATICA, EDGAR A.; CAVASOTTO, CLAUDIO N.

Phoenix, AZ

Conferencia; Annual Biomedical Research Conference for Minority Students; 2009

Virtual screening, the process of docking a large virtual chemical library against a biomolecular target, usually neglects protein flexibility.  One strategy to account for this is to use multiple receptor conformations.  Thus, the structural variations among different proteins simulate the structural changes of a flexible protein. This provides a more real scenario of protein-ligand interactions, which is helpful for structure-based drug discovery.  In a different context, multiple receptor conformations are used in “inverse” docking, a method in which a single small molecule is docked against a large library of receptors.  This method is useful for finding the molecular target for a biologically active molecule (potential drug, toxin, biological modulator, etc.). Although these two approaches are promising, both are relatively new, and still require extensive validation prior to widespread use.