Effect of pressure on the solution structure and hydrogen bond properties of aqueous N-methylacetamide

Highlights: ► NMA molecules are associated mostly through their hydrophobic methyl groups. ► High pressure reduces association propensity causing dispersion of these moieties. ► Orientational polarization of vicinal water molecules near O and H atoms of NMA. ► NMA prefers to be a H-bond acceptor rather than a donor in interaction with water. ► Energy of these hydrogen bonds reduces slightly at high pressure. -- Abstract: Effects of high pressure on hydrophobic and hydrogen bonding interactions are investigated by employing molecular dynamics (MD) simulations of aqueous N-methylacetamide (NMA) solutions. Such systems are of interest mainly because high pressure causes protein denaturation and NMA is a computationally effective model to understand the atomic-level picture of pressure-induced structural transitions of protein. Simulations are performed for five different pressure values ranging from 1 atm to 8000 atm. We find that NMA molecules are associated mostly through their hydrophobic methyl groups and high pressure reduces this association propensity, causing dispersion of these moieties. At high pressure, structural void decreases and the packing efficiency of water molecules around NMA molecules increases. Hydrogen bond properties calculations show favorable NMA–NMA hydrogen bonds as compared to those of NMA–water hydrogen bonds and preference of NMA to be a hydrogen bond acceptor rather than a donor in interaction with water.