Sampling saddle points on a free energy surface.
Many problems in biology, chemistry, and materials science require knowledge of saddle points on free energy surfaces. These saddle points act as transition states and are the bottlenecks for transitions of the system between different metastable states. For simple systems in which the free energy depends on a few variables, the free energy surface can be precomputed, and saddle points can then be found using existing techniques. For complex systems, where the free energy depends on many degrees of freedom, this is not feasible. In this paper, we develop an algorithm for finding the saddle points on a high-dimensional free energy surface "on-the-fly" without requiring a priori knowledge the free energy function itself. This is done by using the general strategy of the heterogeneous multi-scale method by applying a macro-scale solver, here the gentlest ascent dynamics algorithm, with the needed force and Hessian values computed on-the-fly using a micro-scale model such as molecular dynamics. The algorithm is capable of dealing with problems involving many coarse-grained variables. The utility of the algorithm is illustrated by studying the saddle points associated with (a) the isomerization transition of the alanine dipeptide using two coarse-grained variables, specifically the Ramachandran dihedral angles, and (b) the beta-hairpin structure of the alanine decamer using 20 coarse-grained variables, specifically the full set of Ramachandran angle pairs associated with each residue. For the alanine decamer, we obtain a detailed network showing the connectivity of the minima obtained and the saddle-point structures that connect them, which provides a way to visualize the gross features of the high-dimensional surface.
Program in Applied and Computational Mathematics, Princeton University, Princeton, New Jersey 08544, USA.
Amit
A
Samanta
Department of Chemistry, New York University, New York 10003, USA.
Ming
M
Chen
Courant Institute of Mathematical Sciences, New York University, New York 10003, USA.
Tang-Qing
TQ
Yu
Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, New York 10003, USA and Institute for Pure and Applied Mathematics, 460 Portola Plaza, Los Angeles, California 90095, USA.
Mark
M
Tuckerman
BICMR and School of Mathematical Sciences, Peking University, Beijing, China and Department of Mathematics and Program in Applied and Computational Mathematics, Princeton University, Princeton, New Jersey 08544, USA.
Weinan
W
E