New CABS-dock method enables protein-peptide docking without prior knowledge of the binding site

By Sebastian Kmiecik, Researcher at the Laboratory of Theory of Biopolymers, University of Warsaw

Researchers from the Laboratory of Theory of Biopolymers at the University of Warsaw have developed CABS-dock, a new computational method (available as a web server) which allows predicting the structure of protein-peptide complexes and uses no knowledge about the peptide binding site nor the peptide conformation. The method utilizes highly efficient simulation approach for molecular docking of peptides to proteins.

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 (like Rosetta FlexPepDock or HADDOCK) 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 dataset cases, high or medium accuracy models were obtained (sufficient for practical applications). The performance summary is presented in the Figure below.




Figure caption. CABS-dock performance summary for 103 bound and 68 unbound benchmark cases. The percentages of high-, medium- or low-accuracy models (high accuracy: rmsd<3 Å; medium accuracy: 3 Å ≤ rmsd ≤ 5.5 Å; low accuracy: rmsd > 5.5 Å) are reported for the best quality models found in the sets of 10 000 models (all) and in the sets of 10 final models (top 10). Figure is taken from the CABS-dock paper [Nucleic Acids Res, 2015, doi: 10.1093/nar/gkv456]. Entire benchmark results are available in the online CABS-dock materials at

Additionally, as optional features, CABS-dock enables to 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

Article: Mateusz Kurcinski, Michal Jamroz, Maciej Blaszczyk, Andrzej Kolinski, Sebastian Kmiecik, CABS-dock web server for flexible docking of peptides to proteins without prior knowledge of the binding site, Nucleic Acids Research, 2015. doi: 10.1093/nar/gkv456

Supplementary video:


Video description: An example simulation of protein-peptide molecular docking using CABS-dock web server. In the movie, the assembly of major histocompatibility complex (MHC)-peptide structure is simulated. Experimental peptide structure is shown in green, while the simulated peptide in red. The movie shows 1 of 10 trajectories generated in a standard CABS-dock simulation run. The predicted peptide structure, shown at the simulation end, differs from the experimental structure by 1.8 Ångstroms.


CAPRI 5th evaluation meeting

The CAPRI 5th evaluation meeting has just finished last week.

Unfortunately I couldn’t attend this year.

Fortunately, you can get the spirit of the meeting from this series of 3 blog posts over at Grid-Cast:

Combining and conquering at the CAPRI 5th evaluation meeting

Proteins by design – expanding on nature

Wrapping up at CAPRI – beers, bikes and brainstorming

The current CAPRI round is all about peptide docking! Exciting!

If anyone came back from the meeting please share your impressions.

Written by Nir London in: Events | Tags: , ,

Deriving Inhibitory Peptides from Globular Protein–Protein Interactions

There are several forms of peptide-protein interactions, one of which are globular PPIs mediated by a dominant linear peptide at the interface. To what extent could peptides extracted from a globular protein monomer be used to inhibit the interaction to its partner? In this work, we have investigated the possibility of deriving peptides from the interface of globular proteins to design inhibitors that would compete with their native interaction.


Sub-angstrom modeling of complexes between flexible peptides and globular proteins

We present Rosetta FlexPepDock, a novel tool for refining coarse peptide–protein models that allows significant changes in both peptide backbone and side chains. We obtain high resolution models, often of sub-angstrom backbone quality, over an extensive and general benchmark of 89 peptide–protein interactions.


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