Molecular Dynamics Study on Protein and it's Water Structure at High Pressure

Abstract

We have performed NPT molecular dynamics simulations (Langevin Piston Method) on two types of solvated proteins-"denaturation-unfavorable" protein (insulin) and "denaturationfavorable protein" (ribonuclease A) at high pressure (from 1 bar up to 20 kbar). The method is based on the extended system formalism introduced by Andersen, where the deterministic equations of motion for the piston degree of freedom are replaced by Langevin equation. We report the structural changes of proteins (ribonuclease A and insulin) and water molecules through radius of gyration, solvent accessible surface area, hydrogen bond pattern, and the topology of water clusters connected by the hydrogen bonded circular network. The solvent accessibility of ribonuclease A is mainly decreased by hydrophilic residues rather than hydrophobic residues under high pressure. From the results of hydrogen bond analysis, we have found that a-helix is more stable than P-sheet under high pressure. In addition, from the analysis of the water cluster, we have observed that for ribonuclease A, 5-membered ring structure is more favorable than 6-membered ring at higher pressure. However, for insulin, the ratio of 5 to 6-ring is constant over the pressure ranges for which we have performed M D simulation. This indicates that the water structure around insulin does not change under high pressure.

Temperature–pressure stability of green fluorescent protein: A Fourier transform infrared spectroscopy study

“…Most proteins have a unfolding transition midpoint around 5–6 kbar. The high‐pressure stability of wtGFP and its mutants has only been observed in few other cases, such as insulin (Dirix, personal communication;38, bovine pancreatic trypsin inhibitor (BPTI),39, 40 and ribonuclease P2 from Sulfolobus solfataricus 41. The respective molecular weights of these latter proteins are 5.7, 6.5, and 7 kDa.…”

Porcine parvovirus VP1/VP2 on a time series epitope mapping: exploring the effects of high hydrostatic pressure on the immune recognition of antigens

“…HHP and low temperature HHP simulations displayed small fluctuations during the production run and only the N-terminal region of the VP2 1K3V structure showed changes in configuration (amino acids . Compared with the molecular dynamics of native VP2, the HHP simulation tended to produce fixed turns where interconversion between bends and turns were recorded (amino acids [45][46][47][48][49][50][51][52][53][54][55] whereas low temperature HHP fixed this region in a 3-helix configuration. The region from amino acids 75-85 fluctuated among alpha-helix/turn/3-helix configurations in the native simulation but the region was then fixed as an alpha-helical structure in the HHP run and varied between turns and bends in the low temperature HHP run.…”

“…The contributions from studies on the dynamics of capsid autoassembly in vitro and in silico have provided interesting insights into the behavior of such ensembles. As illustrated by Silva et al [14] and tested in silico in a number of conditions [55][56][57], the use of HHP methods alters the distribution of forces in the viral capsid to promote an energy compliant structure; this treatment results in a tangible output as epitopes revealed by this method are of great interest for both diagnostics and basic research.…”

Sensitivity of Water Dynamics to Biologically Significant Surfaces of Monomeric Insulin: Role of Topology and Electrostatic Interactions

“…[12] In the same year, Chai and Jhon performed molecular dynamics study on interfacial hydration structure surrounding Insulin molecule at high pressure. [13] Since then the molecular dynamics simulations have become much more accurate and powerful. Moreover, the timescales in which studies can be performed have improved greatly since and a detailed dynamical study can now be carried out.…”

“…Moreover, the timescales in which studies can be performed have improved greatly since and a detailed dynamical study can now be carried out. While the water structure around Insulin has been studied by Chai et al and Badger et al [13,14], to the best of our knowledge, no prior study exist that has evaluated the dynamics of interfacial water surrounding Insulin and the connecting role of such "biological water" with the structural morphology of the two distinct surfaces of Insulin.…”