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

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

 

Happy April 1! Announcing Cyrus ROSVAC-4!

Seattle, WA, April 1 2019. Cyrus Biotechnology is proud to announce a major step forward in computer biochemistry, the ROSVAC-4, an industrial-strength minicomputer custom-designed for simulations of biological molecules, with an astonishingly small 1900 sq ft. footprint, capable of over 10 simultaneous protein amino acid sequence calculations per annum, improving on ROSVAC-2 at 5 calculations per annum.
UNIVAC-I1951
Data is input into ROSVAC-4 using our proprietary PROTTAPES, custom-designed tape input and storage appliances capable of over 100 bytes per second data storage, recording an atomic protein structure in mere hours! ROSVAC-4 displays protein cartoon structures in beautiful 128×128 black and white pixels (ROSVAC-4 operator control booth pictured below). ROSVAC-4 requires a minimal staff of 5 technicians and 3 data entry staff, along with 1 glassblower and a part-time blacksmith for routine repairs.
Univac_w_prot
“The best part is how easy it is to use! I just startup the generator, rebuild the broken vacuum tubes, initiate startup procedures, finalize boot loading, set switches 7 through 1028 and then press the red button and turn the key” said ROSVAC-4 beta tester Steve Smith of the USAF. “Three months later I have results I can use.”.
“Why run on the cloud when you can have a ROSVAC-4 installed on-site in a dedicated room for only a few million bucks?”, says user John Jacobs at General Electric, “last time I checked its not raining!”.
Cyrus is taking orders for ROSVAC-4 now! Installation at your facility complete in 12-18 months. Prices start at only $15 million, and support contracts are available. Cyrus is also offering a 6 month training course at ROS-U for corporate technicians.
Thanks for reading! If it is not already clear, Cyrus is not really launching a ROSVAC-4, but we offer a best-in-class cloud-based protein modeling and design tool, Cyrus Bench based on Rosetta, with a set of new features released over the end of 2018 and early 2019 including arbitrary small molecule modeling (for small molecule discovery, e.g. more accurate modeling of drug/protein interactions) and antibody structure prediction. Learn more at our web site or Contact us at info@cyrusbio.com if you would like to watch a demo or get a quote.

Cyrus Biotechnology Exhibits at the PEGS Protein Engineering Summit in Boston, April 8th – 11th

March 26, 2019

SEATTLE, March 26, 2019 — Cyrus Biotechnology, Inc., a biotechnology software company offering advanced protein modeling and design tools to the Biopharmaceutical, Synthetic Biology, Chemical, and Consumer Products industries is pleased to announce its participation in the 15th Annual PEGS Boston Protein Engineering Summit in Boston, from April 8th through April 11th.

Dr. David Pearlman, Senior Fellow and Director of Customer Experience at Cyrus Bio, and Rosario Caltabiano, Executive VP of Sales, will attend the conference and discuss the latest advances in in silico protein engineering at booth 539 in the Boston Seaport World Trade Center Exhibit Hall.

Cyrus Biotechnology offers commercial tools based on the well-known Rosetta protein design package. The company is a spin out of David Baker’s laboratory at the University of Washington, established to make these tools easier to deploy and use. Cyrus has implemented the Rosetta platform with an easy to use interface on a computing cloud, resulting in high reliability software with high performance, usability and security. Cyrus Bench® software, and the underlying Rosetta software package, are already leveraged by many global pharmaceutical organizations, and Cyrus customers can apply the most advanced and validated in silico protein engineering science through an intuitive user interface for:

  • Protein Structure Prediction (best overall performance at CASP and CAMEO)
  • Antibody Structure Prediction from Sequence
  • Protein Stabilization
  • Computational Affinity Maturation (Interface Design)
  • Fast Free Energy Calculations
  • Prediction of Immunogenic Epitopes
  • Removal of Identified Liabilities
  • Protein Structure Optimization and Design
  • Antibody Engineering
  • Antigen Design
  • Enzyme Design and optimization

About Cyrus Biotechnology Inc.

Cyrus Biotechnology, Inc. is a privately-held biotechnology software company offering Cyrus Bench®, a Software-as-a-Service (SaaS) platform for protein modeling and design capabilities 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 the laboratory of Prof. David Baker 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.

Cyrus Biotechnology Chief Science Officer Yifan Song to Speak at BAGIM – Boston Area Group for Informatics and Modeling

SEATTLE, WA March 11, 2019 — Cyrus Biotechnology, Inc., a Seattle-based biotech software company commercializing the advanced protein design platform Rosetta announced today that Dr Yifan Song, Cyrus Bio Chief Scientific Officer, will speak at an upcoming meeting of the Boston Area Group for Informatics and Modeling (BAGIM).

Topic: Got Structure? State-of-the-art protein structure prediction with homology modeling

Date: Thursday, March 14th, 2019

Time: 6:00 PM EDT

Venue: Shire – 125 Binney St, Cambridge, MA 02142

Event on Meetup: https://www.meetup.com/Boston-Area-Group-for-Informatics-and-Modeling/events/259399520/

Abstract:

Most computational methods that can be applied during drug discovery require a protein structure. Ideally, such structures are derived from experimental approaches such as X-ray, EM or NMR. However, frequently, an experimental structure of the specific protein of interest is not available. In such a case we turn to homology modeling.

The state-of-the-art for homology model prediction has progressed tremendously over the past two decades. Whereas useful HM models were initially only available in cases where a high-similarity homolog was available in the PDB, it is now often possible to predict such models even when the best homologs have only 15-25% similarity to the sequence whose structure is being predicted. The dramatic improvement in what is possible with HM is due to several factors, including: adoption of methods that can identify suitable low similarity templates on the basis of Markov Models, familial and other deep analysis of sequence space; the ability to incorporate multiple low-similarity templates to broadly span a target sequence; powerful approaches to model building that can handle missing structure due to lack of template, insertions and deletions; and the availability of massive compute power through processor clusters and parallelization. In many cases, the HM models that can be generated are so good—not only in terms of backbone trace, but also in such fine details as hydrogen bonding network, salt bridges, disulphide bonds, etc.—that they are suitable for downstream modeling methods.

We will present the history of HM approaches, culminating in a description of the state-of-the-art Rosetta HM workflow.


For more information on Cyrus Bench, click here.

About BAGIM (Boston Area Group for Informatics and Modeling)
BAGIM is an active community of Boston area scientists bringing together people from diverse fields of modeling and informatics to impact life and health sciences. BAGIM strives to create a forum for great scientific discussions covering a wide range of topics including data management, visualization, computational chemistry, drug discovery, protein structure, molecular modeling, structure-based drug design, data mining, software tools, and the sharing of goals and experiences. Our community is made up of participants from academia, government, and/or industry whose goal is to engage in the discussion of science involving a synthesis of theory and technology. Discussions sponsored by BAGIM are targeted to the needs and interests of informatics scientists, computational chemists, medicinal chemists, and statisticians. BAGIM also provides opportunities for networking within these disciplines as well as an arena for the dissemination of information of specific interest to the membership.
http://bagim.org

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

Cyrus Biotechnology Announces Release of Antibody Structure Prediction Software for Biologics Drug Development and Discovery

SEATTLE, WA March 5, 2019 — Cyrus Biotechnology, Inc., a Seattle-based biotech software company commercializing Rosetta, an advanced protein design platform, announced today the release of a novel Antibody Structure Prediction Software tool as part of its Cyrus Bench® platform.

“Antibodies make up the majority of Biologics, and now Cyrus users can model new antibodies in Bench®” said Cyrus CEO Dr. Lucas Nivon. “Antibody modeling in Rosetta was pioneered by a number of laboratories, especially that of Dr. Jeffrey Gray at Johns Hopkins University, but those methods have remained difficult to access. Our new offering makes these applications significantly more robust and easier to use, so both laboratory biochemists and antibody engineers can rely on them.”

Rosetta software is the world leader in protein modeling and design. Now, the most up-to-date protocols in Rosetta for antibody modeling are available in Bench®, facilitating work on a wider variety of common monoclonal antibody engineering problems. When combined with Cyrus’ protein modeling tools for predicting how protein mutations affect stability and affinity, these antibody prediction tools make possible complex workflows for improving efficacy or reducing potential liabilities in candidate antibody biologics.

The Rosetta antibody tools, successfully validated in the Antibody Modeling Assessment (AMA-II), have now been extended to accept a broader range of inputs without user intervention. Cyrus’ implementation uses machine learning to improve the accuracy of the antibody structure prediction workflow.

The new antibody homology modeling software is now available to subscribers to Cyrus Bench® and to new customers who subscribe to the Cyrus Bench® suite of tools.

https://www.businesswire.com/news/home/20190305005035/en/Cyrus-Biotechnology-Announces-Release-Antibody-Structure-Prediction

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.

Cyrus Contact – Lucas Nivon

lucas@cyrusbio.com

206-258-6561

Cyrus Bio announces full release of rapid and accurate protein mutational free energy tool in Cyrus Bench

Seattle, WA, January 7, 2019 – Cyrus Biotechnology, Inc., a Seattle-based firm offering access to Rosetta, the most advanced and validated software available for protein modeling and accelerated drug discovery, announced today the general release of an improved tool to predict the effect of sequence mutations on protein stability. This new software allows Cyrus customers to easily and rapidly triage thousands of potential mutations for a candidate protein molecule, in turn reducing the time and expense of experimentation. The result is more efficient discovery of stable, active, and effective Biologic drugs and other proteins.

The new mutational free energy software, herewith termed “ddG II”, replaces the existing free energy ddG tool in Cyrus Bench®. All current customers have immediate access to ddG II, and new customers can access this function simply by subscribing to the Cyrus Bench® suite of tools. 

The result of several years of work, ddG II improves on the original ddG calculation approach in Rosetta and Bench in a number of ways, including: 

  • More precise control of atomic movement
  • An improved Rosetta energy function
  • New algorithms to optimize mutations to and from proline. 

The new method has been benchmarked across a newly curated set of over 750 mutations chosen to evenly represent a broad range of different types of mutational changes. 

  • On this new benchmark set, ddG II provides a 20% improvement in rank ordering over the original ddG, as measured by the Predictive Index(1)
  • It improves categorization, as evaluated by the AUC from ROC analysis(2)
  • It reduces the number of egregious errors by more than 50%. 

As with the original ddG method, algorithmic efficiency and the significant parallelization accessible via Bench allow hundreds of ddG II calculations to be run per hour. 

Details of the original version of this approach are found in Park et al. 2016(3), and the new benchmarking and refinements will be expanded upon in a forthcoming publication focused specifically on the ddG II algorithm.

The newly curated benchmark set has been critical to the development of ddG II. In order to create this new set, Cyrus scientists examined existing datasets of protein mutational free energy changes and identified two significant issues with those datasets: 

  1. They tend to be overweighted by a handful of mutation types, particularly mutations to Alanine. 
  2. Some of the data suffers sign inconsistencies. 

The new dataset has been curated to address both of the above issues and then used to tune the algorithms now available as ddG II. One intuitive way to measure the accuracy of a free energy change is simply by categorization – experimentally measured values that are negative should be predicted by the algorithm as negative, positive as positive, neutral as neutral. By such a categorization measure, ddG II is significantly improved and is quantitatively better across a wide range of accuracy metrics.  

By improving accuracy while maintaining extremely high speed and throughput, and by retaining the simple graphical user interface for this method in Cyrus Bench®, these free energy capabilities are now more useful to a much broader set of scientists in both industry and academia. For example, it is very common to screen mutations using parallelized experimental methods that integrate approaches such as robotics or high throughput spectroscopic screening. However, – even the most efficient of these experimental methods require weeks or months to carry out. By contrast, the ddG module in Cyrus Bench® can evaluate thousands of variants in a day, thereby drastically reducing both the number of mutants that need to be tested experimentally and the time required to carry out this testing.

By combining speed and accuracy, researchers can use ddG in Bench to quickly test thousands of mutations, so they can focus their experimental efforts on a small set of variants instead — saving time and money while identifying better molecules in the process. These methods do not replace all work in the lab, but they make the experimentation process much more efficient, enabling more rapid discovery of valuable molecules. 

  1. Pearlman DA & Charifson P (2001) J Med Chem 44 3417-3423
  2. Fawcett T (2006) Pattern Recognition Letters 27 861–874
  3. Park H, Bradley P, Greisen P Jr, Liu Y, Mulligan V K, Kim D E, Baker D & DiMaio F (2016) J Chem Theory and Comput 12 6201-6212

Cyrus Biotechnology Inc.

Cyrus Biotechnology, Inc. is a privately-held biotechnology software company offering Cyrus Bench®, a Software-as-a-Service (SaaS) platform for protein modeling and design capabilities to accelerate discovery of biologics and small molecules for the Biotechnology, Pharmaceutical, Chemical, Consumer Products and Synthetic Biology industries.  Cyrus Bench® is based primarily on the Rosetta software from the laboratory of Prof. David Baker at the University of Washington, the only protein engineering software experimentally proven to design new proteins completely via software. 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, the W Fund, and others. For more information please visit