TY - CHAP
T1 - Information-Driven, Ensemble Flexible Peptide Docking Using HADDOCK
AU - Geng, Cunliang
AU - Narasimhan, Siddarth
AU - Garcia Lopes Maia Rodrigues, João
AU - Bonvin, Alexandre M J J
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Protein-peptide docking
KW - Flexibility
KW - Information-driven docking
KW - Ensemble docking
KW - HADDOCK
KW - Molecular dynamics simulations
U2 - 10.1007/978-1-4939-6798-8_8
DO - 10.1007/978-1-4939-6798-8_8
M3 - Chapter
C2 - 28236236
VL - 1561
T3 - Methods in Molecular Biology
SP - 109
EP - 138
BT - Modeling Peptide-Protein Interactions
A2 - Schueler-Furman, Ora
A2 - London, Nir
PB - Springer
CY - New York
ER -