Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water.

Sidney Elmer, Sanghyun Park, & Vijay S. Pande.
Journal of Chemical Physics (2005)

SUMMARY: Here, we lay out some of the first applications of a new method for future FAH calculations. This new method, Markovian State Models (MSM), allows FAH to solve some important limitations of previous methods. Since these limitations are most relevant for larger and more complex systems than what has been done in FAH so far, this does not affect the work in the past. However, it lays the foundation for FAH to tackle even more complex and challenging problems.

TECHNICAL ABSTRACT: In this article, we analyze the folding dynamics of an all-atom model of a polyphenylacetylene (pPA) 12-mer in explicit solvent for four common organic and aqueous solvents: acetonitrile,chloroform, methanol, and water. The solvent quality has a dramatic effect on the time scales in which pPA 12-mers fold. Acetonitrile was found to manifest ideal folding conditions as suggested by optimal folding times on the order of ~100-200 ns, depending on temperature. In contrast,
chloroform and water were observed to hinder the folding of the pPA 12-mer due to extreme solvation conditions relative to acetonitrile; chloroform denatures the oligomer, whereas water promotes aggregation and traps. The pPA 12-mer in a pure methanol solution folded in ~400 ns at 300 K, compared relative to the experimental 12-mer folding time of ~160 ns measured in a 1:1 v/v THF/methanol solution. Requisite in drawing the aforementioned conclusions, analysis techniques based on Markov state models are applied to multiple short independent trajectories to extrapolate the long-time scale dynamics of the 12-mer in each respective solvent. We review the theory of
Markov chains and derive a method to impose detailed balance on a transition probability matrix computed from simulation data.