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

• Published in: Journal of computer-aided molecular design Vol. 38; no. 1; p. 38
• Main Authors: Phougat, Monika, Sahni, Narinder Singh, Choudhury, Devapriya
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2024; Springer Nature B.V
• Subjects: Acetonitrile; Acetonitriles - chemistry; Amino acids; Animal Anatomy; Atomic properties; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Histology; Hydrophobic and Hydrophilic Interactions; Mixtures; Molecular dynamics; Molecular Dynamics Simulation; Morphology; Organic solvents; Peptides; Peptides - chemistry; Physical Chemistry; Proteins; Simulation; Solvation; Solvents; Solvents - chemistry; Surface area; Temperature dependence; Tessellation; Voronoi graphs; Water - chemistry; Kirkwood-Buff integrals; Contact surface area; Preferential solvation; Voronoi tessellation; way Partial Least Squares; Molecular Dynamics simulation; Preferential hydration; N-way Partial Least Squares
• ISSN: 0920-654X; 1573-4951; 1573-4951
• DOI: 10.1007/s10822-024-00579-9

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 ACN  = 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.