|
|
|
|
|
|
| About Jose Duca (Schering-Plough) |
|
Born in Córdoba, Argentina, José Duca received his BS in Physical Organic Chemistry in 1990 and a PhD in Chemistry in 1995 from the National University of Córdoba. In 1997 he moved to Chicago where he joined the Molecular Modeling and Design group led by Prof. Tony Hopfinger in the College of Pharmacy at the University of Illinois at Chicago. José spent 2.5 winters as a postdoctoral fellow. He joined the Schering-Plough Research Institute in 2000, where he currently is a Principal Scientist in the Department of Drug Design. His scientific fields of expertise within computational chemistry include – but are not limited to – molecular modeling, ab initio calculations, molecular recognition, QM-MM methods and structure-based drug design.
|
|
Cross-docking vs. Scoring: Is Overfitting the Third Wheel?
José Duca, Schering-Plough Research Institute
Addressing protein flexibility has been a shortcoming of many methods. In this study, we used cross-docking of ~150 inhibitors into the full set of crystal structures for each inhibitor complexed with the kinase CDK2. In scoring relative binding potency based on multiple combinations of several target proteins, the dangers of over-fitting became apparent. Examples will be given of insights gained into ligand properties such as pKa values and relative tautomeric stabilities computed via ab initio quantum mechanical methods.
|
|
|
|
|
|
|
|
|
