Studies of Large Conformational Changes in Biomolecular Machines

PI Name: 
Benoit Roux
PI Email:
The University of Chicago
Allocation Program: 
Allocation Hours at ALCF: 
55 Million
Research Domain: 
Biological Sciences

Proteins are extremely complex tiny "molecular machines". Their concerted action underlies many of the critical activities of living organisms. Membrane-associated proteins play an essential role in controlling the bi-directional flow of material and information. Malfunction of some critically important proteins can often lead to diseases such as cancer.

This project is aimed at gaining a deep mechanistic perspective of such protein function, linking structure to dynamics, by characterizing the free energy landscape that governs the key functional motions. Src tyrosine kinases and the ATP-driven ion pumps will be studied within a unified computational perspective provided by free energy landscapes. As a benchmark for quantifying the accuracy of the approach, the conformational propensity of small peptides in solution will also be studied.

By studying experimentally well-characterized systems of increasing size and complexity within a unified theoretical framework based on free energy landscapes, we will push the envelope and advance the theory-modeling-simulation (TMS) technology. TMS offers a virtual route to address fundamental biological questions and help solve the problem of rational protein design. The computations planned for this project will serve as a “road-map” for simulating, visualizing and elucidating how biomolecular nano-machines membrane proteins work.