CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site

TL;DR

CABS-dock is a web server that enables flexible, blind docking of peptides to proteins without prior knowledge of the binding site, achieving high accuracy in diverse cases.

Contribution

It introduces a novel flexible docking protocol that does not require predefined binding sites and is validated on the largest dataset of protein-peptide interactions.

Findings

Achieved high or medium accuracy in over 80% of cases

Validated on the largest non-redundant dataset to date

Allows optional flexibility adjustments for receptor and binding modes

Abstract

Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock doesn't require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound data set cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock