CVC Seminar Web Mar 9, 1:30-3pm, ACES 4.304

Maysam Moussalem

Molecular docking: current approaches and remaining challenges

Docking is defined as the prediction of the correct relative pose of a protein-protein, protein-ligand or protein-RNA complex given the individual molecules’ coordinates derived from their crystal structures. Algorithms are made up of three main components: flexibility models for the receptor and ligand, a search algorithm to explore conformational and positional space, and a scoring function to assess intermolecular affinity.

While docking is currently being used with some success for rapid screening of large databases of known drugs for lead identification, it is less successful at recovering the exact relative pose the drug takes with respect to the target as well as determining their binding affinity. The two biggest unsolved challenges in molecular docking which limit its application to lead optimization are: (1) accurate and efficient modeling and exploration of proteins’ large number of degrees of freedom, which would result in better pose prediction, and (2) improved accurate and efficient scoring functions which are capable of distinguishing correct binding poses from false ones for large varieties of target-drug combinations.

In this talk, we will present current methods and discuss how they attempt to tackle these difficulties as well as where they fall short.