SBIR Phase II: Computer-Directed High Throughput Screening for Improved Enzymatic Activity

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This Small Business Innovation Research (SBIR) Phase II project focuses on the development of an enabling technology for computer- directed high-throughput screening of proteins with improved properties. Xencor's Protein Design Automation (PDA) predicts all the possible amino acid sequences that will fold into the three-dimensional structure of a protein. There should be molecules among those sequences that have the structure and function of the "parent "protein, together with additional novel properties such as increased thermo-stability or alkaline pH optima. In Phase I the company addressed this possibility using xylanase as a model protein. After targeting the active site of the enzyme for PDA re-design, the company found sequences that were more active than the wild-type protein and one that had a different pH profile. These results were achieved by testing only 260 of a possible 110,592 sequences. In Phase II the company will develop a high-throughput assay system that will allow testing the majority of the predicted sequences. The research will also improve electrostatic functions of the PDA algorithm, and then use this version of the program to re-design the entire xylanase molecule instead of just the active site, thereby finding mutations located away from the active site that effect the protein's characteristics.The PDA technology improves enzyme efficiency and expands the reactions and process conditions where they can be applied. Major markets include polymer manufacturers, value extraction from waste streams and food processing.