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 are highly flexible, powerful, and capable of performing a wide range of functions. However, these platforms are also complicated and difficult to use, requiring significant knowledge to be wielded effectively. In addition, they require specialized software and hardware systems, which places a high technical burden on installation and maintenance for non-expert users. All these factors make it unlikely that CPD will become a standard tool for experimentalists who want to engineer novel proteins. In order to make CPD accessible to bench scientists, Protabit will develop a web-based, easy-to-use, commercial platform for protein engineering called TriadWeb. This web-based platform will build on Triad, Protabit's existing software suite for protein engineering, which was developed in collaboration with Caltech and Monsanto. The objectives of this Phase I project are: (1) develop a suite of web-based apps that harness the full power of CPD in a simple, easy-to-understand way; (2) develop the back-end software infrastructure to enable a cloud-based web-service with user authentication and encryption; (3) couple TriadWeb with a secure, user-partitioned dataserver to assist in the organization, sharing, and querying of project data; and (4) incorporate dynamic, interactive visualization tools to assist in viewing and interpreting data and results. With TriadWeb, the web browser will gather the minimal necessary input needed to 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 complex protein design simulations, all running on specialized hardware maintained either by Protabit or in a cloud environment. The results will be provided visually to the bench scientist in the form of 3D molecular renderings, charts and graphs where possible. 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 smart phones and iPads. The overall objective of this Phase I proposal and the follow-on Phase II proposal is to provide bench scientists with a usable suite of apps that translate complex CPD functions into simple easy-to-learn procedures.
Engineered proteins such as therapeutic antibodies and specialized enzymes for drug manufacturing are making significant contributions to improved 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, that will substantially accelerate the discovery of valuable engineered proteins.
