Peptide docking

Best practice guide

HADDOCK supports docking of peptides as well. Since the secondary structure of short peptides is not always well defined, is is safer to dock an ensemble of multiple conformations. Different ways of generating of these conformations are described here. More documentation about peptide docking with HADDOCK is in following sections:

Tutorials
Publications
Optimal settings for docking of peptides
FAQ

Tutorials

HADDOCKing of the p53 N-terminal peptide to MDM2: This tutorial introduces protein-peptide docking using the HADDOCK web server. It also introduces the CPORT web server for interface prediction, based on evolutionary conservation and other biophysical properties.

Publications

C. Geng, S. Narasimhan, J. P.G.L.M. Rodrigues and A.M.J.J. Bonvin. Information-driven, ensemble flexible peptide docking using HADDOCK. Methods in Molecular Biology: Modeling Peptide-Protein Interactions. Eds Ora Schueler-Furman and Nir London. Humana Press Inc. 1561, 109-138 (2017).
A.D. Spiliotopoulos, P.L. Kastritis, A.S.J. Melquiond, A.M.J.J. Bonvin, G. Musco, W. Rocchia and A. Spitaleri. dMM-PBSA: a new HADDOCK scoring function for protein-peptide docking. Frontiers in Molecular Biosciences, 3:46 doi:10.3389/fmolb.2016.00046 (2016).
E. Deplazes, J. Davies, A.M.J.J. Bonvin, G.F. King and A.E. Mark. On the Combination of Ambiguous and Unambiguous Data in the Restraint-driven Docking of Flexible Peptides with HADDOCK: The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion channel (ASIC)1a. J. Chem. Inf. and Model. 56, 127-138 (2016).
J.P.G.L.M. Rodrigues, A.S.J. Melquiond and A.M.J.J. Bonvin. Molecular Dynamics Characterization of the Conformational Landscape of Small Peptides: A series of hands-on collaborative practical sessions for undergraduate students. Biochemistry and Molecular Biology Education, 44, 160-167 (2016).
M. Trellet, A.S.J. Melquiond and A.M.J.J. Bonvin. Information-driven modelling of protein-peptide complexes. Methods in Molecular Biology. Ed. Peng Zhou. Humana Press Inc. 221-239 (2015)
M. Trellet, A.S.J. Melquiond and A.M.J.J. Bonvin. A Unified Conformational Selection and Induced Fit Approach to Protein-Peptide Docking PLoS ONE, 8(3) e58769 (2013). –> ERRATUM

Optimal settings for docking of peptides

Parameter	run.cns name	default value	optimal value
Clustering method	`clust_meth`	FCC	RMSD
Cutoff for clustering	`clust_cutoff`	0.6	5
Number of MD steps for rigid body high temperature TAD	`initiosteps`	500	2000
Number of MD steps during first rigid body cooling stage	`cool1_steps`	500	2000
Number of MD steps during second cooling stage with flexible side-chains at interface	`cool2_steps`	500	4000
Number of MD steps during third cooling stage with fully flexible interface	`cool3_steps`	500	4000

More about optimal settings for different docking scenarios can be found here.

FAQ

Any more questions about peptide docking with HADDOCK? Have a look at our HADDOCK bioexcel forum hosted by . There is a very high chance that your problem has already been addressed.