Information-Driven, Ensemble Flexible Peptide Docking Using HADDOCK

Cunliang Geng, Siddarth Narasimhan, João Garcia Lopes Maia Rodrigues, Alexandre M J J Bonvin

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

Abstract

Modeling protein-peptide interactions remains a significant challenge for docking programs due to the inherent highly flexible nature of peptides, which often adopt different conformations whether in their free or bound forms. We present here a protocol consisting of a hybrid approach, combining the most frequently found peptide conformations in complexes with representative conformations taken from molecular dynamics simulations of the free peptide. This approach intends to broaden the range of conformations sampled during docking. The resulting ensemble of conformations is used as a starting point for information-driven flexible docking with HADDOCK. We demonstrate the performance of this protocol on six cases of increasing difficulty, taken from a protein-peptide benchmark set. In each case, we use knowledge of the binding site on the receptor to drive the docking process. In the majority of cases where MD conformations are added to the starting ensemble for docking, we observe an improvement in the quality of the resulting models.

Original languageEnglish
Title of host publicationModeling Peptide-Protein Interactions
Subtitle of host publicationMethods and Protocols
EditorsOra Schueler-Furman, Nir London
Place of PublicationNew York
PublisherSpringer
Pages109-138
Number of pages30
Volume1561
ISBN (Electronic)978-1-4939-6798-8
DOIs
Publication statusPublished - 2017

Publication series

NameMethods in Molecular Biology
PublisherHumana Press
Volume1561
ISSN (Electronic)1940-6029

Keywords

  • Protein-peptide docking
  • Flexibility
  • Information-driven docking
  • Ensemble docking
  • HADDOCK
  • Molecular dynamics simulations

Fingerprint

Dive into the research topics of 'Information-Driven, Ensemble Flexible Peptide Docking Using HADDOCK'. Together they form a unique fingerprint.

Cite this