Advancing Design & Structure Prediction of Proteins & Peptides

PI Name: 
David Baker
Institution: 
University of Washington
Allocation Program: 
INCITE
Allocation Hours at ALCF: 
5.715 Million
Year: 
2019
Research Domain: 
Chemistry

Researchers from the University of Washington’s Baker lab have pioneered the prediction of protein structure and the design of new amino acid sequences that enable new proteins folds and functions. Past INCITE allocations have improved the accuracy and versatility of Rosetta, the software suite for modeling biomolecular structures that forms the core of the team’s workflow, opening new frontiers in the rational design of macromolecular materials, catalysts, and therapeutics.

The researchers currently have three specific aims: (1) to improve the Rosetta software’s energetic model, with a particular focus on enhancing the accuracy of their design algorithms; (2) to improve the design algorithms themselves, with applications to materials, catalysts, and therapeutics; and (3) to generalize their energy model and algorithms to permit the design of protein-like synthetic heteropolymers bearing capabilities far beyond those of natural proteins.

This INCITE project will allow for rapid cycles that validate improvements made to the team’s method, as well as for applications to real-world problems in materials science and medicine. The impact will be the creation of larger molecules more specific to their targets than their smaller counterparts, ultimately yielding more potent drugs with fewer side effects.