Towards Breakthroughs in Protein Structure Calculation and Design

PI Name: 
David Baker
PI Email:
University of Washington
Allocation Program: 
Allocation Hours at ALCF: 
150 million
Research Domain: 

Proteins are large, complex molecule that drive virtually all cellular functions in living organisms. With the emergence of protein structure modeling tools, researchers have the capability to design proteins with targeted applications, such as treating diseases and catalyzing medically and industrially useful reactions. While progress is continually being made with such tools, the ability to sufficiently sample the vast conformational space remains a limiting factor.

The Rosetta software suite, developed at the University of Washington’s Baker Laboratory, is designed to tackle to two difficult computational problems: the prediction of protein structure from amino acid sequences, and the design of new amino acid sequences to yield a desired function. With this multiyear INCITE project, researchers are using Mira to enhance Rosetta’s ability to adequately sample the conformational space and address other emerging challenges in protein structure calculation and design. Only large supercomputers like Mira have the capacity and rapid interprocess communication ability to consider large numbers of conformational states simultaneously, in parallel, and to permit a sufficiently fast search for an optimal sequence.

The team’s work includes improving the Rosetta energy function and further developing homology model refinement methods. In addition, the researchers are using Mira to design therapeutic peptides with unique, rigid folds that can bind to targets of interest, including influenza and other pathogens.

The overall goal of this project is to develop and apply new computational methods to better understand biomolecular structures and their function with atomic-level precision. Ultimately, this work will allow researchers to design new proteins to address challenges in medicine, energy, and technology.