Correlation between protein conformations and water structure and thermodynamics at high pressure: A molecular dynamics study of the Bovine Pancreatic Trypsin Inhibitor (BPTI) protein

Abstract

Pressure-induced perturbation of protein structure leading to its folding-unfolding is an important yet not fully understood phenomenon. The key point here is the role of water and its coupling with protein conformations as a function of pressure. In the current work, using extensive molecular dynamics simulation at 298K we systematically examine the coupling between protein conformations and water structure for pressures 1 bar, 5, 10, 15, and 20 kbar, starting from (partially) unfolded structures of the protein Bovine Pancreatic Trypsin Inhibitor (BPTI). We also calculate localized thermodynamics at those pressures as a function of protein-water distance. Our findings show that both protein-specific and generic effects of pressure are operating. In particular, we found that (1) The amount of in- crease in water density near the protein depends on the protein structural heterogeneity, (2) the intra-protein hydrogen bond decreases with pressure while the water-water hydrogen bond per water in the first solvation shell (FSS) increases. Protein-water hydrogen bonds were also found to increase with pressure, (3) with pressure hydrogen bonds in the FSS get twisted, (4) Water's tetrahedrality in the FSS decreases with pressure but it is dependent on the local environment. Thermodynamically, at higher pressure, the structural perturbation of BPTI is mainly due to pressure-volume work, while the entropy decreases with the increase of pressure due to higher translational and rotational rigidity of waters in the FSS. The local and subtle effects of pressure, found in this work, are likely to be typical of pressure-induced protein structure perturbation.

Changes in advanced protein structure during dense phase carbon dioxide induced gel formation in golden pompano surimi correlate with gel strength

“…As a result, the protein is in a stretched state, which promotes the interaction between protein molecules (Sikka FIGURE 9 Correlation between protein structure and gel strength during DPCD-induced gel formation (Ib: Ionic bond, Hb: Hydrogen bond, Hi: Hydrophobic interaction, Dcb: Disulfide covalent bond, NDcb: Non-disulfide covalent bond). al., 2008;Roy and Bandyopadhyay, 2023). The reduction in the number of hydrogen bonds also exposes additional hydrophobic groups.…”

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

“…The differences may include multiple mutants of the same protein, 1 multiple substrates of the same enzyme, 2 or under conditions of varying pH, 3 temperature, 4 or pressure. 5 A very large number of independent simulations become necessary if synergistic interactions between two or more variable parameters are under study. Results from multiple independent simulations may first be interpreted individually and the conclusions from each simulation then somehow integrated to obtain a general result.…”

“…In recent years, it has become commonplace to simultaneously interpret multiple molecular dynamics (MD) simulations of biomolecules, each carried out under slightly different conditions. The differences may include multiple mutants of the same protein, multiple substrates of the same enzyme, or under conditions of varying pH, temperature, or pressure . A very large number of independent simulations become necessary if synergistic interactions between two or more variable parameters are under study.…”