ALCF Science 1 - Argonne National Laboratory

argonne leadership computing facility
Chemistry
Simulation of Large Conformational Transitions
in Macromolecular Systems Using Leadership Computing
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 leadershipcomputing
resources such as Argonne’s Blue Gene/P.
of the voltage-gated Kv1.2
potassium channel, a membraneassociated
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.
ALCC Allocation:
28.5 Million Hours
ASCR LEADERSHIP
COMPUTING CHALLENGE
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
13
(a) A snapshot of the atomic model of
the isolated Kv1.2 VSD in the active (up)
configuration from MD simulations in explicit
water-membrane environment
(b) End-states of the VSD conformational transition for the VSD,
from MD simulations: top row, side view; bottom row, extracellular
view; positively charged residues on helix S4 are colored in blue,
while acidic residues on helices S1, S2 and S3 are in red.
Contact Benoit Roux
The University of Chicago/Argonne National Laboratory | roux@uchicago.edu