Effects of osmolytes on the helical conformation of model peptide: Molecular dynamics simulation

Abstract

Co-solvents such as glycerol and sorbitol are small organic molecules solvated in the cellular solutions that can have profound effects on the protein structures. Here, the molecular dynamics simulations and comparative structural analysis of magainin, as a peptide model, in pure water, 2,2,2-trifluoroethanol∕water, glycerol∕water, and sorbitol∕water are reported. Our results show that the peptide NMR structure is largely maintained its native structure in osmolytes-water mixtures. The simulation data indicates that the stabilizing effect of glycerol and sorbitol is induced by preferential accumulation of glycerol and sorbitol molecules around the nonpolar and aromatic residues. Thus, the presence of glycerol and sorbitol molecules decreases the interactions of water molecules with the hydrophobic residues of the peptide, and the alpha helical structure is stabilized.

Sensitivity-Enhanced NMR Reveals Alterations in Protein Structure by Cellular Milieus

“…Cryoprotected NM fibers at 83 K had a chemical shift distribution that was dramatically shifted towards alpha helical values, consistent with sequence-based secondary structural predictions for the M domain(Chou and Fasman, 1974; Cuff et al, 1998; Kumar, 2013). This change is likely a result of secondary structural stabilization effects from the low experimental temperature and the cryoprotectant (Mehrnejad et al, 2011; Vagenende et al, 2009). In contrast, cryoprotected NM fibers that had been polymerized in cellular lysates had a chemical shift distribution that was dramatically shifted away from alpha helical values and towards beta sheet values (Figure 3).…”

Effect of sorbitol and glycerol on the stability of trypsin and difference between their stabilization effects in the various solvents

“…Different mechanisms have been attributed to the stabilizing effect of these two cosolvents. These mechanisms include preferential hydration, preferential exclusion from the denatured protein, and coating effect . However, the molecular basis of these mechanisms is still under debate.…”

Polarizable Empirical Force Field for Acyclic Polyalcohols Based on the Classical Drude Oscillator

“…Molecular dynamics (MD) simulations using classical force field methods have proven to be very useful in the study of structure, dynamics, and thermodynamics of complex systems at the atomic level, and can shed light on this issue. Many MD simulations have been performed on systems containing polyols . Most of these simulations focus on the conformations of polyols in gas, crystal, liquid, or glass states, or their impact on water structure in solutions.…”

“…Most of these simulations focus on the conformations of polyols in gas, crystal, liquid, or glass states, or their impact on water structure in solutions. Very recently, simulation studies were undertaken to investigate the interactions between polyols and peptides/proteins …”