Multiway Analysis Reveals Hydrophobicity as the Sole Determinant of Dynamic Peptide-Acetonitrile-Water Association Behavior.

Multiway analysis, a class of techniques developed for the purpose of studying multi-dimensional multivariate data, has been applied to study the dynamical structure of the first solvation layer of Ace-Gly-X-Gly-Nme peptides (where X is any amino acid) perturbed with the increase in concentrations of acetonitrile. Separate MD simulations of each peptide were carried out in five different concentrations of acetonitrile. Association of peptide, water, and acetonitrile atoms was quantified in terms of the relative abundance of Delaunay tetrahedra whose vertices could be centered on either the peptide, acetonitrile, or water atoms. A three-way data set comprising nine types of Delaunay tetrahedra in the first dimension, five concentrations of acetonitrile in the second dimension, and 26 different peptides in the third dimension was subjected to two different multiway methods viz., the constrained PARAFAC and the unconstrained Tucker3 analysis. The results unequivocally show that the dynamic peptide-acetonitrile-water association behavior could be solely explained by the hydrophobicity of the central amino acid. The study also demonstrates the utility of multiway analysis for the integration and interpretation of large number of separate MD simulations.