|Title:||Generalized Coordinates from Molecular Dynamics Simulations: Reaction Pathways and Dimensionality Reduction|
Theoretical and Computational Biophysics Department
Max Planck Institute for Biophysical Chemistry
Progresses in computer hardware and software allow all-atom molecular
dynamics (MD) simulations to be applied to increasingly large and complex
biological systems. However, most problems of interest (conformational
transitions in macromolecules, protein folding, etc^E) occur on timescales which
cannot be accurately sampled by such methods, due to the very large number of
degrees of freedom involved. Reducing the representation of the system to a few
relevant generalized coordinates which capture the properties of interest thus
remains highly desirable. Exploring the conformational subspace spanned by the
reduced coordinates provides insight into conformations that would be sampled
at much longer simulation times. Sampling can also be selectively enhanced
along one or several of the coordinates, accelerating the associated transition
to simulation-accessible timescales.
However, finding a relevant set of global coordinates is usually not a trivial task. Two examples are presented in this talk. The flipping of a base in DNA, a ubiquitous process occurring on the millisecond timescale, is found to be best described using a generalized reaction coordinate extracted from a principal component analysis. Sampling along this coordinate is enhanced using the conformational flooding technique, yielding the pathway and associated free energy profile. By combining competitive learning and topology-preserving mapping techniques, we attempt to provide optimal reduced-dimensional representations of all-atom MD simulations of small protein systems. These retain the salient features contained in the MD trajectories, facilitating classification and prediction of the possible conformations of the macromolecules.