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

J Comput Aided Mol Des. 2024 Nov 13;38(1):38. doi: 10.1007/s10822-024-00579-9.

Abstract

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 χACN = 0.1-0.9. The preferential solvation parameter (Γ) calculated using the Kirkwood-Buff integral method was used for the assessment of peptide interactions with water/ACN. Additionally, weighted Voronoi tessellation was applied to obtain a three-way data set containing four time-averaged contact surface area types between peptide atoms and water/ACN atoms. A mathematical technique known as N-way Partial Least Squares (NPLS) was utilized to anticipate the preferential interactions between peptides and water/ACN from the contact surface areas. Furthermore, the temperature dependency of peptide-solvent interactions was investigated using a subset of 10 amino acids representing a range of hydrophobicities. MD simulations were conducted at five temperatures, spanning from 283 to 343 K, with subsequent analysis of data focusing on both preferential solvation and peptide-solvent contact surface areas. The results demonstrate the efficacy of utilizing contact surface areas between the peptide and solvent constituents for successfully predicting preferential interactions in water/ACN mixtures across various ACN concentrations and temperatures.

Keywords: N-way Partial Least Squares; Contact surface area; Kirkwood-Buff integrals; Molecular Dynamics simulation; Preferential hydration; Preferential solvation; Voronoi tessellation.

MeSH terms

  • Acetonitriles* / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Dynamics Simulation*
  • Peptides* / chemistry
  • Solvents* / chemistry
  • Water* / chemistry

Substances

  • Acetonitriles
  • acetonitrile
  • Water
  • Solvents
  • Peptides