Prediction of protein mutational free energy: benchmark and sampling improvements increase classification accuracy

SEATTLE, WA March 20, 2020 — Software to predict the change in protein stability upon point mutation is a valuable tool for a number of biotechnological and scientific problems. To facilitate the development of such software and provide easy access to the available experimental data, the ProTherm database was created. Biases in the methods and types of information collected has led to disparity in the types of mutations for which experimental data is available. For example, mutations to alanine are hugely overrepresented whereas those involving charged residues, especially from one charged residue to another, are underrepresented. ProTherm subsets created as benchmark sets that do not account for this often underrepresented certain mutational types. This issue introduces systematic biases into previously published protocols’ ability to accurately predict the change in folding energy on these classes of mutations. To resolve this issue, we have generated a new benchmark set with these problems corrected. We have then used the benchmark set to test a number of improvements to the point mutation energetics tools in the Rosetta software suite.

https://www.biorxiv.org/content/10.1101/2020.03.18.989657v1

Authors:

Brandon Frenz, Steven Lewis, Indigo King, Hahnbeom Park, Frank DiMaio, Yifan Song

About Cyrus Biotechnology

Cyrus Biotechnology, Inc. is a privately-held Seattle-based biotechnology software company offering software and partnerships for protein engineering to accelerate discovery of biologics and small molecules for the Biotechnology, Pharmaceutical, Chemical, Consumer Products and Synthetic Biology industries. Cyrus methods are based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington and HHMI, the most powerful protein engineering software available. Cyrus customers include 13 of the top 20 Global Pharmaceutical firms and is financed by leading investors in both Technology and Biotechnology, including Trinity Ventures, Orbimed, Springrock Ventures, Alexandria Venture Investments, and W Fund.

https://cyrusbio.com

Contacts
Cyrus Biotechnology, Inc.
Lucas Nivon, 206-258-6561
lucas@cyrusbio.com

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Cyrus Biotechnology and the Broad Institute of MIT and Harvard Launch Multi-Target Collaboration to Develop Optimized CRISPR Gene Editing Technology

CAMBRIDGE, Mass. & SEATTLE — Cyrus Biotechnology, Inc., and the Broad Institute of MIT and Harvard have embarked on a scientific collaboration to optimize CRISPR for use in developing novel human therapeutics.

CRISPR allows for the highly specific and rapid modification of DNA in a genome, which can dramatically accelerate the drug discovery process.

Feng Zhang will be the principal investigator for the Broad for the collaboration. He is also an investigator of the Howard Hughes Medical Institute (HHMI).

Together, researchers from Cyrus and Broad will work together to mitigate the possibility of the body mounting an immune response against CRISPR. The teams are committed to making the results of their collaboration broadly available for research to help ensure that therapeutic development — bringing this technology to the clinic — has the best chance of success, while also considering important ethical and safety concerns. The teams have also committed to publishing their results in peer reviewed journals and to make this work freely available to the non-profit and academic scientific community.

Issi Rozen, chief business officer at the Broad Institute, said, “Broad researchers and their collaborators have pioneered the development and sharing of new genome editing tools, such as CRISPR-Cas9, which are revolutionizing and accelerating nearly every aspect of disease research and drug discovery around the world. With this collaboration, scientists will continue to improve the technology towards new tools and therapeutics, important to benefiting patients in the long term.”

Cyrus CEO Dr. Lucas Nivón added, “We have validated our computational deimmunization platform in a variety of systems, and now seek to apply it where it can make a major impact. Given the extensive therapeutic possibilities of CRISPR systems, and the leading position the Broad Institute and Dr. Zhang hold, we are very excited to work in partnership with them to make these molecules more amenable for use in humans with maximal efficacy and minimal side effects.”

Cyrus provides commercial and partnered access to Rosetta, which is the world’s leading protein modeling and design software platform. Rosetta has been used to direct the computational design of multiple biologic molecules that have advanced to both pre-clinical and clinical development. Among these are drugs being developed by companies including PVP Biologics, Tocagen, Lyell and others.

https://www.businesswire.com/news/home/20191202005078/en/Cyrus-Biotechnology-Broad-Institute-MIT-Harvard-Launch

About Cyrus Biotechnology

Cyrus Biotechnology, Inc. is a privately-held Seattle-based biotechnology software company offering software and partnerships for protein engineering to accelerate discovery of biologics and small molecules for the Biotechnology, Pharmaceutical, Chemical, Consumer Products and Synthetic Biology industries. Cyrus methods are based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington and HHMI, the most powerful protein engineering software available. Cyrus customers include 13 of the top 20 Global Pharmaceutical firms and is financed by leading investors in both Technology and Biotechnology, including Trinity Ventures, Orbimed, Springrock Ventures, Alexandria Venture Investments, and W Fund.

https://cyrusbio.com

Contacts
Cyrus Biotechnology, Inc.
Lucas Nivon, 206-258-6561
lucas@cyrusbio.com

Cyrus Biotechnology Offers CryoEM Services based on First-in-class, Peer-reviewed Rosetta Software Methods

SEATTLE, WA August 27, 2019 — Cyrus Biotechnology, Inc., a Seattle-based biotech software company specializing in the use and commercialization of Rosetta, the world’s leading computational protein design platform, announces the availability of CryoEM services to generate high precision models from CryoEM data.

“Over the last several years, CryoEM has emerged as the key new structural method across drug discovery, from small molecules to vaccines,” notes Cyrus CEO Dr. Lucas Nivon. “Our customers have been asking for the powerful and complex CryoEM structure determination and refinement capabilities of Rosetta, which we are now providing via consulting services to Cyrus customers.”

Several publications have demonstrated that Rosetta CryoEM refinement yields far better structures than those obtained from other software methods, including key results in Nature Methods and PNAS.

Rosetta offers state-of-the art refinement, model docking into density, and de novo model building for a broad range of CryoEM map resolutions. Combined with demonstrably superior homology modeling predictions, Rosetta can go from map and sequence to full atomic-level accuracy models.

Customers without the resources or expertise to use CryoEM Rosetta structure solution and refinement tools can now take advantage of Cyrus CryoEM Services, which draw from Cyrus in-house expertise from multiple co-authors of these cutting-edge Rosetta/CryoEM methods.

Cyrus CryoEM services include: structure refinement into density, model building de novo, partial model building, and model building with modifications such as carbohydrates. Cyrus partners with leading laboratories to gather CryoEM data if a customer does not have such facilities. Read more at https://cyrusbio.com/cryoem/

Cyrus CryoEM services can be offered immediately. Please contact us to request a proposal: https://cyrusbio.com/request-cryoem-services/

https://www.businesswire.com/news/home/20190827005088/en/Cyrus-Biotechnology-Offers-CryoEM-Services-Based-First-in-class

About Cyrus Biotechnology

Cyrus Biotechnology, Inc. is a privately held biotechnology software company offering scientific consulting services and the Cyrus Bench® SaaS platform for protein engineering to accelerate discovery of biologics and small molecules for the Biotechnology, Pharmaceutical, Chemical, Consumer Products and Synthetic Biology Industries. Cyrus services are based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington. Rosetta is the most powerful protein engineering software available. Cyrus customers include 13 of the top 20 Global Pharmaceutical firms. The company is financed by leading investors in both Technology and Biotechnology, including Trinity Ventures, Orbimed, Springrock Ventures, Alexandria Venture Investments, and W Fund.

https://cyrusbio.com/

Cyrus Contact – Lucas Nivon

lucas@cyrusbio.com

206-258-6561

Cyrus Biotechnology Significantly Expands Customer Engagement through Biotherapeutic Partnerships and Fee-for-Service Scientific Consulting

SEATTLE, WA August 14, 2019 — Cyrus Biotechnology, Inc., a Seattle-based biotech software company specializing in the use and commercialization of Rosetta, the world’s leading computational protein design platform, announces a significant expansion of its efforts to leverage the full range of Rosetta’s capabilities to establish biotherapeutic partnerships and offer fee-for-service consulting to its customers.

“Over the last couple of decades, Rosetta has emerged as the most validated and comprehensive software for the computational design of proteins, leading to multiple biomolecules now in pre-clinical and clinical trials from companies such as PVP Biologics, Tocagen, Lyell and others” notes Cyrus CEO Dr. Lucas Nivon. “Our customers have been eager to more closely collaborate with Cyrus on their most strategic R&D challenges, which can be addressed by Rosetta’s vast capabilities well beyond the features currently available in the Cyrus Bench software. As a result, we have decided to make a set of services available with focus on Pharma discovery needs.”

The new services include: difficult homology modeling, highly parallelized docking and modeling/design for biologics and vaccines, modeling and design of large protein or protein/nucleic acid complexes, structure building and refinement for CryoEM and X-Ray crystallography, protein stabilization and solubilization (Rosetta and machine learning based), and a range of other services based on Cyrus in-house tools.

While substantially expanding its capacity to support collaborative partnerships and consulting services, Cyrus will reduce the velocity of its efforts to incorporate Rosetta capabilities into its Cyrus Bench software, which will continue to be maintained and supported to the benefit of its customers with the basic set of Rosetta capabilities. Cyrus Bench customers will be able to expand their relationship with Cyrus to tackle a broader set of challenges through Cyrus fee-for-service scientific consulting.

Cyrus has already established partnerships with downstream revenue-sharing components and has successfully engaged in several fee-for-service projects with small biotechs, global pharmaceuticals, synthetic biology and consumer product companies. Cyrus can leverage Rosetta and its scientific expertise in the discovery and development of antibodies, non-antibody biologics, therapeutic enzymes (e.g. Enzyme Replacement Therapy), signalling proteins, peptides, vaccines and a variety of applications in computer-assisted small molecule discovery.

https://www.businesswire.com/news/home/20190815005705/en/Cyrus-Biotechnology-Significantly-Expands-Customer-Engagement-Biotherapeutic

About Cyrus

Cyrus Biotechnology, Inc. is a privately-held biotechnology software company offering scientific consulting services and the Cyrus Bench® SaaS platform for protein engineering to accelerate discovery of biologics and small molecules for the Biotechnology, Pharmaceutical, Chemical, Consumer Products and Synthetic Biology industries. Cyrus services are based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington. Rosetta is the most powerful protein engineering software available. Cyrus customers include 13 of the top 20 Global Pharmaceutical firms. The company is financed by leading investors in both Technology and Biotechnology, including Trinity Ventures, Orbimed, Springrock Ventures, Alexandria Venture Investments, and W Fund.

https://cyrusbio.com/

Cyrus Contact – Lucas Nivon

lucas@cyrusbio.com

206-258-6561

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