Monoclonal antibodies and other protein-based therapeutics represent a $100+ billion and growing market with broad applications in the treatment of cancer, metabolic diseases, and other human disorders. Thus, any technology that facilitates the discovery of useful protein variants will have a major impact in biology and medicine; application areas include drug discovery, small molecule screening, and the development of new diagnostics and reagents. One such enabling technology that has been under active development in the last decade is computational protein design (CPD). Current CPD platforms and auxiliary tools are highly flexible, powerful, and capable of performing a wide range of functions. However, these platforms are also complex, difficult to use, and require significant knowledge to be applied effectively. In addition, they require specialized software and hardware systems, which place a high technical burden on installation and maintenance for non- expert users. All these factors inhibit CPD adoption as a standard tool for experimentalists who want to engineer novel proteins. In order to make CPD accessible to bench scientists, Protabit is developing a web-based, easy-to-use, unified, commercial platform for protein engineering called TriadWeb. TriadWeb builds on Triad, Protabit's existing state of the art software suite for protein engineering, which was developed in collaboration with Caltech and Monsanto. We have made significant progress in Phase I and will continue development with the following objectives in Phase II: (1) port all remaining functions from Triad into TriadWeb; (2 improve the user interface beyond the Phase I accomplishments with workflows, wizards, and a visual molecular editor; (3) interface with useful databases, enable user annotations, and automatically generate reports; and (4) engage academia as users and provide TriadWeb as a publishing platform. Fortunately, the field of CPD has advanced to the point where many CPD functions can be packaged as applications in much the same manner as the applications that are routinely found on mobile devices. With TriadWeb, the web browser will gather high-level input and suggest new protein sequence libraries that can then be expressed and assayed in the lab for desired properties. This input will be gathered using concepts readily understandable to bench scientists. TriadWeb will convert these high level directives into protein design simulations that run on specialized hardware maintained either by Protabit or in a cloud environment. The results will be presented to the bench scientist in readily understandable format via an integrated molecular visualizer, tables, and graphs. By tightly integrating with a database, TriadWeb will also provide project management, a file server, collaboration, reproducibility, and report generation. When complete, TriadWeb will provide bench scientists with a usable suite of apps that translate complex CPD functions into simple easy-to- learn procedures.

Public Health Relevance

Engineered proteins such as therapeutic antibodies, enzymes for drug manufacturing, and proteins used to identify new small molecule drugs are making significant contributions to improve health care. The goal of the proposed research is to make complex computational protein engineering tools more accessible to the bench scientist. Protabit will achieve this objective through the development of a web-based computational tool, TriadWeb, which will substantially accelerate the discovery of valuable engineered proteins.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1)
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Wu, Mary Ann
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Protabit, LLC
United States
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