title: Closing the side-chain gap in protein loop modeling.
abstract: The success of structure-based drug design relies on accurate protein modeling where one of the key issues is the modeling and refinement of loops. This study takes a critical look at modeled loops, determining the effect of re-sampling side-chains after the loop conformation has been generated. The results are evaluated in terms of backbone and side-chain conformations with respect to the native loop. While models can contain loops with high quality backbone conformations, the side-chain orientations could be poor, and therefore unsuitable for ligand docking and structure-based design. In this study, we report on the ability to model loop side-chains accurately using a variety of commercially available algorithms that include rotamer libraries, systematic torsion scans and knowledge-based methods.
authors.affiliation: Bristol-Myers Squibb Company, Research & Development, Computer-Assisted Drug Design, P.O. Box 5400, Princeton, NJ 08543, USA. karen.rossi@bms.com
authors.forename: Karen A
authors.initials: KA
authors.lastname: Rossi
authors.forename: Akbar
authors.initials: A
authors.lastname: Nayeem
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Weigelt
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Krystek
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D015195:Drug Design; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: D011506:Proteins