CovPepDock Server Documentation


CovPepDock is a tool for designing peptide binders that form an irreversible covalent bond with a target cysteine, starting from a known non-covalent binder.

As input, the user should provide a PDB structure of a peptide-protein complex, and specify the target cysteine and peptide chain. The protocol identifies all the peptide positions that are in close proximity to the target cysteine, and mutate each of these positions to various electrophiles. It then performs docking simulations for each of these putative peptides, using the Rosetta FlexPepDock application, with the addition of constraints that favors the formation of a covalent bond between the electrophile and the target cysteine. As output, the protocol provides a list of the most promising peptide candidates.


The results page provides a list of the peptide modifications that are identified by the protocol as the most promising candidates for irreversible binding. The candidates are selected based on their interface score, covalent constraint score and backbone interface RMSD. For each peptide candidate, we display a PyMol visualization of the top-interface-scoring model of that modification, as well as the values of the aforementioned scoreterms of that model.


Please cite the following article when referring to results from our ROSIE server:

  1. TBA

  2. Lyskov S, Chou FC, Conchúir SÓ, Der BS, Drew K, Kuroda D, Xu J, Weitzner BD, Renfrew PD, Sripakdeevong P, Borgo B, Havranek JJ, Kuhlman B, Kortemme T, Bonneau R, Gray JJ, Das R., "Serverification of Molecular Modeling Applications: The Rosetta Online Server That Includes Everyone (ROSIE)". PLoS One. 2013 May 22;8(5):e63906. doi: 10.1371/journal.pone.0063906. Print 2013. Link

We welcome scientific and technical comments on our server. For support please contact us at Rosetta Forums with any comments, questions or concerns.

CovPepDock was developed by the London lab at WIS.