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

https://xconomy.com/national/2019/12/03/a-safer-crispr-cyrus-broad-institute-look-to-quell-concerns/

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https://www.fiercebiotech.com/biotech/cyrus-broad-team-up-to-make-vivo-crispr-use-safer

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https://www.geekwire.com/2019/cyrus-biotechnology-teams-crispr-pioneers-boost-gene-editing-therapies/

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

Cyrus Biotechnology featured in BIOCENTURY article on de novo Protein Design Revolution

SEATTLE, WA July 29, 2019 — Cyrus Biotechnology, Inc., a Seattle-based biotech software company commercializing Rosetta, the most advanced computational protein design platform, has been mentioned in the BIOCENTURY’s article:

Institute for Protein Design’s de novo revolutionHow a Seattle hub is overhauling protein- and cell-based therapies by breaking free o evolution’s constraints.

The BIOCENTURY article can be found here.

About Cyrus Biotechnology
Cyrus Biotechnology, Inc. is a privately-held biotechnology software company offering Cyrus Bench®, a 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 Bench® is based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington, the most powerful protein engineering software available. Cyrus customers include 12 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/

Cyrus Biotechnology Protein Engineering Scientist Amanda Duran to Speak at Precision Medicine & Ion Channel Retreat 2019

SEATTLE, WA July 26, 2019 — Cyrus Biotechnology, Inc., a Seattle-based biotech software company commercializing Rosetta, the most advanced computational protein design platform, announced today that Dr Amanda Duran, Cyrus Bio Protein Engineering Scientist, will speak at the Precision Medicine & Ion Channel Retreat in Vancouver, British Columbia, Canada.

DETAILS:

Title: Functional and Mutational Analysis with Rosetta and Cyrus Bench: KCNQ1 case study

Date: Friday, July 26th, 2019

Time: 2:40 PM PDT

Venue: Sheraton Vancouver Wall Centre

PMICR 2019 Program

http://www.aurorabiomed.com/wp-content/uploads/2019/07/Final-2019-Program-1.pdf

ABSTRACT:

Ion channels are one of the largest drug targets likely due to their role in regulation and signal transduction. KCNQ1 is a voltage-gated potassium channel associated with cardiac arrhythmias such as Long-QT syndrome. Several structures of the voltage sensing domain (VSD) or the pore domain have been resolved; however, there are no known structures of a resting VSD. In order to understand the mutational effects, the inactive VSD, closed pore state of KCNQ1 was modeled using Rosetta. RosettaCM enables the use of multiple templates in addition to fragment insertion during homology modeling. Knowledge from experimental studies of the charged residue pairing placement in the VSD was used as a filter during model selection. Finally, MolProbity, ProCheck, and PoreWalker were used to further assess the quality of the selected models.

Several methods exist for modeling mutation-induced stability changes from proteins of known structure or homology models; however, many of these methods perform poorly for membrane proteins. The amount of mutant thermostability data that is available for membrane proteins is sparse, making it nearly impossible to train an accurate predictor for the stabilizing effects of mutations. In a membrane protein benchmark, Rosetta outperformed most of the 10 methods assessed and was able to correctly classify nearly 70% of mutations as destabilizing. Combining these modeling efforts may help with identifying disease-associated mutations in the future. Cyrus Bench is capable of rapidly assessing the stabilizing effects of single point mutations using the newest Rosetta scoring function and thoroughly benchmarked protocols.

For more information on Cyrus Bench, click here.

About PMICR 2019
Over the last 16 years, the Precision Medicine and Ion Channel Retreat (PMICR) has evolved into one of the premier conferences for drug discovery, genomics and ion channel research. The 17th annual PMICR strives to continue this proud tradition by providing a platform to explore cutting edge technology and innovative research from around the world. This diverse, thought-provoking event allows academic and industry researchers to share knowledge, exchange ideas and establish fruitful partnerships. The Retreat is designed to maximize networking opportunities, with social events providing an intimate & relaxed atmosphere.

http://www.aurorabiomed.com/precision-medicine-ion-channel-retreat-2019/

About Cyrus Biotechnology
Cyrus Biotechnology, Inc. is a privately-held biotechnology software company offering Cyrus Bench®, a 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 Bench® is based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington, the most powerful protein engineering software available. Cyrus customers include 12 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

Cyrus Biotechnology Integrates DNA/RNA Support into its Rosetta-based Protein Design Platform

SEATTLE, WA May 29, 2019 — Cyrus Biotechnology, Inc., a Seattle-based biotech software company commercializing Rosetta, the most advanced computational protein design platform, is announcing the release of novel software capabilities to handle protein interactions with DNA & RNA as part of its Cyrus Bench® platform.

“Proteins that interact directly with DNA and RNA are part of an increasing number of early discovery pipelines across the BioPharmaceutical industry, ranging from CRISPR proteins to enzymes for DNA synthesis and modification,” notes Cyrus CEO Dr. Lucas Nivon. “At Cyrus we can now accelerate discovery in these key new markets with the newly released DNA/RNA Rosetta protein design capabilities in Cyrus Bench.”

Rosetta software is the world leader in protein modeling and design, with features including homology modeling and design to improve both protein affinity and protein stability. Rosetta combines both physical and statistical/machine learning methods, and differs from all other commercially available modeling software in the breadth of both application and experimental validation. Proteins designed using Rosetta are in pre-clinical or clinical evaluation by companies such as Tocagen, PvP Bio, Sana and Lyell.

These new features in Cyrus Bench® enable accelerated optimization and design of both tool compounds and therapeutic candidates, including polymerases, transcription factors, DNA modifying enzymes (e.g. CRISPRs), RNA modifying enzymes (e.g. isomerases) and other valuable compounds. These targets are critical to such fields as Therapeutics, Diagnostics, Agricultural Biotechnology and Biotechnology Tools.

These new software capabilities are available now to subscribers to Cyrus Bench® and to new customers who subscribe to the Cyrus Bench® suite of tools.

https://www.businesswire.com/news/home/20190529005228/en/Cyrus-Biotechnology-Integrates-DNARNA-Support-Rosetta-based-Protein

 

About Cyrus

Cyrus Biotechnology, Inc. is a privately-held biotechnology software company offering Cyrus Bench®, a 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 Bench® is based on the Rosetta software from Prof. David Baker’s laboratory at the University of Washington, the most powerful protein engineering software available. Cyrus customers include 10 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/

 

Cyrus Contact – Lucas Nivon

lucas@cyrusbio.com

206-258-6561