1. Driven Adiabatic Dynamics Approach to the Generation of Multidimensional
Free-Energy Surfaces.
Mark E. Tuckerman, Dept. of Chemistry, New York University, New York, NY 10003
Predicting the stable structures of complex systems such as biomolecules polymers remains one of the computational grand challenges.
Meeting the challenge would have a significant impact on problems such as protein folding and aggregation. What makes the problem
difficult is the fact that the potential energy function describing the various conformations of the molecule consists of many local minima
separated by barriers that are high relative to the average thermal energy available to each degree of freedom. Hence, standard simulation
techniques, such as molecular dynamics or Monte Carlo, tend to spend inordinately long periods of time in local minima and are able to
cross barriers between minima only very infrequently, so that a complete exploration of the conformational space becomes intractable. We
have introduced a new technique, driven adiabatic free-energy dynamics, that is capable of efficiently mapping out the conformational
free-energy landscape of a complex system using a small set of collective variables. The technique works by introducing a set of driving
variables coupled to the collective variables in a molecular dynamics calculation. These driving variables are then heated, allowing them
to cross high barriers on the potential-energy surface, and assigned a high mass, thereby adiabatically decoupling them from the physical
degrees of freedom. Under these conditions, it can be shown that the free-energy surface is directly related to the probability distribution
function in the driving variables, a quantity that can be easily extracted from the molecular dynamics trajectory. The figure below shows
an example of the alanine hexamer in solution, and the free-energy surface in the number of hydrogen bonds (NH) and radius of gyration
(RG) extracted from a short (5 ns) molecular dynamics calculation. It can be seen that they favored conformation, the α-helix, is rapidly
identified.