The following API services are provided by Cyrus:
Antibody HM creates homology models of antibodies using the Cyrus NextGen Antibody structure prediction method.
This method takes as input an antibody heavy and light chain and returns models of the antibody fV fragment. The Single Chain HM API is a more suitable approach for modeling nanobodies and non-antibody proteins.
Clean PDB is a tool made available to all customers free of charge for preparing PDB files for use by the other Cyrus API tools
DDG is a tool for predicting the energetic consequences of single mutations. It approximates the Gibbs free energy change of folding of the native vs. point mutant.
Disulfidizer is a tool for searching for disulfides. Given an input structure it will attempt to sample disulfides that might exist. This is appropriate for:
Looking for disulfides which will stabilize the conformation of an input structure
Searching for places to put disulfides when no prior hypothesis or suggestion is at hand
Disulfidizer results are reasonably polished (if the –permissive flag is not used), but you may wish to further evaluate disulfides with other computational tools before proceeding to a wet experiment.
Epitope Scan runs an rosetta MHC II epitope prediction algorithm on an input protein structure or sequence. This API uses a machine learning model to predict epitopes based entirely on the sequence of the protein. Structure input is provided as a convenience but the API will produce identical results regardless of whether a sequence or structure is used as input.
Force Disulfide forces the input disulfide to exist and attempts to relax the protein structure in the presence of that chemical bond (simulated as bond-like restraint, not a kinematic imperative). It requires the user to state which disulfides are desired. This tool is appropriate in three cases:
You know this bond forms in nature for this sequence (perhaps from mutational data), have a structure of the sequence without cysteines or disulfides, and want a quick peek at what it might look like
You are doing blue-sky thinking or hypothesis generation about places disulfides could go and want to absolutely force models to have a given disulfide (our other tools will not enforce it so strongly if the energetics dislike it)
You are creating input models for other tools like HM.
Force disulfide results should always be considered preliminary and evaluated with/after other modeling tools.
Loop modeling runs the Rosetta Next Generation KIC loop modeling protocol. This API is useful for modeling loops of between 5 and 17 residues. This tool is suitable for resampling the conformations of existing loops. It is the same underlying tool as our Loop Rebuild Action in Bench; that tool’s documentation contains more details.
Relax runs the Rosetta FastRelax protocol. Quoting from the RosettaCommons documentation: “This finds low-energy backbone and side-chain conformations near a starting conformations by performing many rounds of packing and minimizing, with the repulsive weight in the scoring function gradually increased from a very low value to the normal value from one round to the next.” This is useful for taking a structure not generated by Rosetta and “relaxing” it into the Rosetta scorefunction preparatory to further modeling, or for generating a backbone ensemble for a further modeling experiment.
Single Chain HM is a homology modeling tool for generating a structure prediction for your sequence optimizing structures. This tool adds an additional feature to tell Rosetta where extra disulfides are wanted by the researcher, to cover cases where the templates were not clear. This is appropriate for:
Creating high-quality models of proteins that you have preliminarily modeled by other means, or have experimental reason to believe they exist
Results from Single Chain HM should be considered gold standard results from Rosetta. Further modeling never hurts but is not strictly necessary.
Solubility Scoring predicts the solubility of a protein structure using a method similar to the AGGRESCAN method. This is a structure based method and requires a protein model as input, a high quality homology model generated by the Single Chain HM method is an acceptable input to the Solubility Scoring tool.
Template Predictor runs blast, sparksX, and hhsearch, and returns alignment information which can be useful in determining how well homology modeling will work for the given target.