# Milestoning, Extending Time Scale of Molecular Simulations

Thursday, July 26, 2007 - 9:15am - 9:55am

EE/CS 3-180

Ron Elber (The University of Texas at Austin)

A new computational algorithm to extend time

scales of

atomically detailed simulations is illustrated. The

algorithm

(Milestoning) is based on partitioning the dynamics to a

sequence of

trajectories between “milestones” and constructing a

non-Markovian

model for the motion along a reaction coordinate.

Besides toy models, two molecular systems are discussed:

(i) The

kinetics of a conformational transition in a blocked

alanine is computed

and shown to be accurate, more efficient than

straightforward Molecular

Dynamics by a factor of about 9, and non-exponential. (ii)

The allosteric

conformational transition in Scapharca hemoglobin is

calculated. The

results for the rate (about 10+/-9 microseconds) are in

accord with

experiment and are obtained about 1,000 times faster than

straightforward

Molecular Dynamics. No assumption of an activated process

or states

separated by significant barrier is made.

A general scaling argument predicts linear speed-up with

the number of

milestones for diffusive processes, and exponential

speed-up for

transitions over barriers. The algorithm is also trivial to

parallelize.

As a side result Milestoning also produces the free energy

profile along

the reaction coordinate, and is able to describe

non-equilibrium motions

along one (or a few) degrees of freedom.

scales of

atomically detailed simulations is illustrated. The

algorithm

(Milestoning) is based on partitioning the dynamics to a

sequence of

trajectories between “milestones” and constructing a

non-Markovian

model for the motion along a reaction coordinate.

Besides toy models, two molecular systems are discussed:

(i) The

kinetics of a conformational transition in a blocked

alanine is computed

and shown to be accurate, more efficient than

straightforward Molecular

Dynamics by a factor of about 9, and non-exponential. (ii)

The allosteric

conformational transition in Scapharca hemoglobin is

calculated. The

results for the rate (about 10+/-9 microseconds) are in

accord with

experiment and are obtained about 1,000 times faster than

straightforward

Molecular Dynamics. No assumption of an activated process

or states

separated by significant barrier is made.

A general scaling argument predicts linear speed-up with

the number of

milestones for diffusive processes, and exponential

speed-up for

transitions over barriers. The algorithm is also trivial to

parallelize.

As a side result Milestoning also produces the free energy

profile along

the reaction coordinate, and is able to describe

non-equilibrium motions

along one (or a few) degrees of freedom.