Foldamer dynamics expressed via Markov state models. I. Explicit solvent molecular-dynamics simulations in acetonitrile, chloroform, methanol, and water.
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 approximately 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 approximately 400 ns at 300 K, compared relative to the experimental 12-mer folding time of approximately 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.
Elmer
Sidney P
SP
Department of Chemistry, Stanford University, California 94305-5080, USA.
Park
Sanghyun
S
Pande
Vijay S
VS
D000097:Acetonitriles / Q000737:chemistry*; D000114:Acetylene / Q000737:chemistry*; D002725:Chloroform / Q000737:chemistry*; D003198:Computer Simulation; D008390:Markov Chains; D000432:Methanol / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
D000097:Acetonitriles; D012997:Solvents; D014867:Water; D002725:Chloroform; D000114:Acetylene; D000432:Methanol; C032159:acetonitrile