Understanding the relationship between preferential interactions of peptides in water-acetonitrile mixtures with protein-solvent contact surface area.

The influence of polar, water-miscible organic solvents (POS) on protein structure, stability, and functional activity is a subject of significant interest and complexity. This study examines the effects of acetonitrile (ACN), a semipolar, aprotic solvent, on the solvation properties of blocked Ace-Gly-X-Gly-Nme tripeptides (where Ace and Nme stands for acetyl and N-methyl amide groups respectively and X is any amino acid) through extensive molecular dynamics simulations. Individual simulations were conducted for each peptide, encompassing five different ACN concentrations within the range of χ = 0.

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.