BMERC Seminar: New Directions in Docking and Scoring

When:       Tuesday, May 27, 11:00 am

Where:      ENG room 203, 44 Cummington Street

Title:          New Directions in Docking and Scoring

Speaker:   Dr. Istvan J. Enyedy
Biogen Idec, Cambridge, MA

Abstract: Target structure-based “hit” optimization in a drug discovery project is challenging from the computational point of view. Scoring functions cannot predict binding affinity, thus computational chemists must use their intuition or prior knowledge about the target class to prioritize compounds for synthesis. As the pharmaceutical industry targets novel protein classes, computational chemists must use software to build knowledge about the new targets. Over the last two years we have set up about 300 internal structures and more than 10,000 compounds for testing docking and scoring strategies. We used this set for evaluating the new scoring function CHEMGAUSS5, implemented in FRED and HYBRID from OpenEye, and ATLAS from Acpharis. The talk will focus on how we can guide docking and scoring by using solvent mapping for identifying and characterizing pockets suitable for small molecules. The use of fragment clusters for defining the shape and size of the search space used for docking or shape-based search will be shown. The presentation will highlight the influence of the binding site conformation, size of the search space, and target on the outcome of docking. In the end a comparison of statistical methods used for evaluating the performance of docking and scoring will be presented.