Collaborative Programs
Cyrus has been working for years to expand and enhance the functionality of the Rosetta molecular modeling and protein design package. We have accumulated a set of novel capabilities that can dramatically enhance your work, but which are too complex to be made easily accessible through a Cyrus Bench™ or Engine subscription.
These deep functionalities can be accessed through collaborative partnership with Cyrus, and they bring along with them the full breadth of Cyrus staff expertise – including a founding cohort of Rosetta developers – and the potential to modify and customize software to meet your exact scientific requirements.
Cyrus Partnerships are not fee-for-service arrangements but involve significant and sustained intellectual involvement by Cyrus computational biologists. Although we are very flexible in crafting such partnerships, Cyrus benefits by realizing some of the long-term value created by the collaboration in the form of milestones, royalties and license fees.
Partnership Initiatives
Deimmunization
If you have a protein therapeutic showing evidence of immunogenicity, which could materially impact clinical development, we can identify the responsible epitopes and – most importantly – engineer them out while retaining normal function. We can also reduce or eliminate other key liabilities in development, such as aggregation and thermal instability. Building deimmunization into early protein design will significantly reduce the chances of encountering immunogenicity in preclinical or clinical evaluation, and these approaches can also help to revive a valuable but immunogenic asset.
Small Molecule Drug Discovery
If you are building a virtual screen, the quality of your target model will materially impact the probability of success, and your ability to predict the effects of hits and leads. For high value targets with challenging structures – those that have proven difficult or impossible to crystallize, for example – we can help you build a robust and reliable model which will accurately predict the binding characteristics of your small molecules. This is particularly advantageous where the possession of a unique target model provides you with a strategic advantage. In other cases where crystal structures already exist, Cyrus tools can be used to build various bound or unbound conformational models, to uncover novel binding sites or modes of binding activity, opening up the screen to further innovation.
Vaccine Design
We can redesign vaccine antigens using computational protein design, to improve characteristics such as stability, immunogenicity and antigen presentation. We can also build new antigen display formats employing your desired macro-molecular constructs to maximize likely immune stimulatory effects.
Small Protein and Peptide Design
We can partner with you to create custom software or help discover your own designed small proteins or cyclic peptides. Cyrus has worked with both a discovery-stage Biotech and a top-10 Global Pharma firm to help them discover or optimize novel linear or cyclic peptides, and we have deep internal expertise and custom software infrastructure to execute efficiently on your projects.
CryoEM Structure Determination
Using services from Cyrus you can achieve better results in drug discovery, faster. Rosetta has pioneered major advances in structure determination from cryoEM, including solving models that are otherwise impossible, with key publications in Nature (Walls et al, 2016), Nature Methods (DiMaio et al, 2015) and PNAS (James et al, 2017). Our offerings use a variety of tools in Rosetta to build more accurate and realistic atomic resolution models for your discovery applications, and we can provide full structure determination with experimental data collection and model building with the cryoEM tools in Rosetta. We offer structure refinement, model building into density, model docking into density, homology modeling with cryoEM density, model completion for partly-built models (RosettaES), and full structure determination from cryoEM density and sequence.
