Simulation of Large Conformational Transitions in Macromolecular Systems using Leadership Computing

PI Name: 
Benoit Roux
PI Email:
University of Chicago
Allocation Program: 
Allocation Hours at ALCF: 
28.5 Million
Research Domain: 

Specialized strategies maximize simulation studies of protein gating

Atomistic molecular dynamics (MD) simulations are increasingly helping us to understand complex macromolecular systems. It is, however, essential to develop special strategies to get quantitatively meaningful results that can be compared with experiments. Many questions cannot be addressed with “brute force” MD simulation methods. Special methods and strategies are needed, for example, to treat large-scale motions in macromolecules to best use leadership-computing resources such as Argonne’s Blue Gene/P. 

Novel approaches field tested on Intrepid

In this project, researchers will develop novel and cutting-edge approaches based on the string method with swarms-of-trajectories and Milestoning with Voronoi tessellation for characterizing large conformational transitions in complex macromolecular systems. They will use Intrepid to compute the transition pathway for the activation of the voltage-gated Kv1.2 potassium channel, a membrane-associated protein that functions as a molecular switch. This will be the first “field testing” of this novel and advanced methodology on a large macromolecular system.