Welcome to ROSIE Rosetta Online Server that Includes Everyone

Overview:

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.

Results:

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.

Notes:

• The peptide chain can be up to 20 amino acids long.
• Ligands and non-canonical amino acids are allowed, but may be removed if Rosetta fails to read them (-ignore_unrecognized_res is set to true). Note that modified or non-canonical amino acids on the peptide may not be mutated to electrophiles.
• Modifications of the target cysteine (acetylation, methylation, etc.) are also allowed, as long as the "SG" atom is present. However, these modifications will be removed during docking.
• To avoid errors, the input structure may be renumbered. Pay attention to the different numbering when reviewing the output files.

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.