AnchorDock: Blind and flexible anchor-driven peptide docking

Avraham Ben-Shimon, Masha Y. Niv*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)929-940
Number of pages12
JournalStructure
Volume23
Issue number5
DOIs
StatePublished - 5 May 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ltd.

Fingerprint

Dive into the research topics of 'AnchorDock: Blind and flexible anchor-driven peptide docking'. Together they form a unique fingerprint.

Cite this