High-resolution global peptide-protein docking using fragments-based PIPER-FlexPepDock

• DOI: 10.1371/journal.pcbi.1005905
• Publication Date: 2017-12-27T18:28:07Z
• Authors: Nawsad Alam; Oriel Goldstein; Bing Xia; Kathryn A. Porter; Dima Kozakov; Ora Schueler-Furman
• Keywords: Docking (animal); Protein–ligand docking; Interactome; Macromolecular docking; Fragment (logic)

Peptide-protein interactions contribute a significant fraction of the protein-protein interactome. Accurate modeling these is challenging due to vast conformational space associated with highly flexible peptides large receptor surfaces. To address this challenge we developed fragment based high-resolution peptide-protein docking protocol. By streamlining Rosetta picker for accurate peptide ensemble generation, PIPER algorithm exhaustive fragment-receptor rigid-body and FlexPepDock full-atom refinement docked models, successfully addressed efficient global at remarkable accuracy, as validated on small but representative set complex structures well resolved by X-ray crystallography. Our approach opens up way many more detailed study association in general. PIPER-FlexPepDock freely available academic community server http://piperfpd.furmanlab.cs.huji.ac.il.