AnchorDock: Blind and Flexible Anchor-Driven Peptide Docking.
The huge conformational space stemming from the inherent flexibility of peptides is among the main obstacles to successful and efficient computational modeling of protein-peptide interactions. Current peptide docking methods typically overcome this challenge using prior knowledge from the structure of the complex. Here we introduce AnchorDock, a peptide docking approach, which automatically targets the docking search to the most relevant parts of the conformational space. This is done by precomputing the free peptide's structure and by computationally identifying anchoring spots on the protein surface. Next, a free peptide conformation undergoes anchor-driven simulated annealing molecular dynamics simulations around the predicted anchoring spots. In the challenging task of a completely blind docking test, AnchorDock produced exceptionally good results (backbone root-mean-square deviation ≤ 2.2Å, rank ≤15) for 10 of 13 unbound cases tested. The impressive performance of AnchorDock supports a molecular recognition pathway that is driven via pre-existing local structural elements.
Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment and The Fritz Haber Center for Molecular Dynamics, The Hebrew University, Rehovot 76100, Israel.
Avraham
A
Ben-Shimon
Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment and The Fritz Haber Center for Molecular Dynamics, The Hebrew University, Rehovot 76100, Israel. Electronic address: masha.niv@mail.huji.ac.il.
Masha Y
MY
Niv
D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D008958:Models, Molecular; D062105:Molecular Docking Simulation / Q000379:methods*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software
D010455:Peptides