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Molecular Dynamics Simulations of hydrophobic peptides that form β-hairpin structures in solution

Moharana, T. R.; Nagaraj, R.

2021-10-09 biochemistry
10.1101/2021.10.08.463620 bioRxiv
Show abstract

Peptides designed with residues that have high propensity to occur in {beta}-turns, form {beta}-hairpin structures in apolar solvents as well in polar organic solvents such as dimethyl sulfoxide (DMSO), methanol and varying percentages of DMSO in chloroform (CHCl3). Presumably due to limited solubility, their conformations have not been investigated by experimental methods in water. We have examined the conformations of such designed peptides that fold into well-defined {beta}-hairpin structures facilitated by {beta}-turns, in the crystalline state and in solution, by Molecular Dynamics Simulations (MDS). The peptides fold into {beta}-hairpin structures in water, starting from extended conformation. In DMSO, folding into {beta}-hairpin structures was not observed, starting from extended conformation. However, when the starting structure is in {beta}-hairpin conformation, unfolding is not observed during MDS in DMSO. Water clearly favours folding of short, hydrophobic peptides into {beta}-turn and {beta}-hairpin conformations from extended structures. DMSO does not have a denaturing effect on short, hydrophobic peptides.

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