Effects of co-solvents on peptide hydration water structure and dynamics

Abstract

We evaluate the molecular response of hydration water as a function of temperature and proximity to the surface of the peptide N-acetyl-leucine-methylamide (NALMA) when in the presence of the kosmotrope co-solvent glycerol or the chaotrope co-solvent dimethyl sulfoxide (DMSO), using molecular dynamics simulation with a polarizable force field. These detailed microscopic studies complement established thermodynamic analysis on the role of co-solvents in shifting the equilibrium for proteins away from or towards the native folded state. We find that the structure of the water at the peptide interfaces reflects an increase in hydration number in the glycerol solution and a decrease in hydration numbers in the DMSO solution. While the water dynamics around NALMA in the presence of both co-solvents is slower than that observed with the water solvent alone, in the DMSO mixture we no longer measure a separation in water motion time scales at low temperatures as is seen in the pure water solvent, but rather one single relaxation time. In the glycerol, however, we do observe a separation of time scales at low temperatures, supporting the hypothesis that hydration water near a hydrophobic solute evolves on a separate time scale than the extensive hydrogen-bonding network of more bulk-like water. Our simulation studies highlight the differences in the two co-solvent solutions due to the relative frequency of water contacts with the hydrophobic vs. hydrophilic peptide surface, and direct water interactions with the co-solvents.

A hybrid neutron diffraction and computer simulation study on the solvation of N-methylformamide in dimethylsulfoxide

“…The results showed indicate the formation of a strong H-bond between the O of DMSO and the amine hydrogen in noticeable agreement with experimental results reported previously. 4,5,11 The characteristics shown for this H-bond suggest that NMF might be more strongly H-bonded to DMSO than to water, or, if DMSO is added as co-solute to an aqueous solution of NMF, the water molecules H-bonded to the amine hydrogen would be delocated for it, in line with results reported previously. 9,11 Besides the O(DMSO)-H(NMF) H-bond, the results point to a secondary auxiliary S-HN H-bond, what must collaborate for the structure of the mixture.…”

“…The influence of dimethylsulfoxide (DMSO) on the peptide behavior is an interesting case of chaotropy/kosmotropy. 4,5 It has been shown that at moderate concentrations DMSO enhances enzyme activity (behaves as a kosmotropic agent) by increasing the conformational flexibility of the protein, 6,7 while in other cases the protein functionality was decreased (DMSO behaves as a chaotropic agent) by enhancing the protein rigidity. 8,9 Proteins dissolved in pure DMSO cannot exhibit functional activity because they become unable to adopt the native structure.…”

Evidences for Cooperative Resonance-Assisted Hydrogen Bonds in Protein Secondary Structure Analogs

“…1 (NMF and NMA) as protein secondary structure analogs22232425. Another molecule used in our study is dimethyl sulphoxide (DMSO), which is known to interact strongly with proteins/peptides2627 and to be a good water-miscible solvent to improve the solubility of hydrophobic compounds in water28, so that is applied widely in biochemistry2930. In addition, DMSO can also work as cryo-protectant3132, cell fusogen333435, cell differentiation inducer3637, and membrane/skin permeation enhancer.…”

Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival

“…[10][11][12] Polyols (such as glycerol) have been used as cryoprotectants for proteins, functionally stabilizing protein structure by maintaining hydrogen bonding in protein-bound water. 13,14 Amino acids have been utilized for liposomal cryopreservation, 15,16 and ampholytic amino acid polymers have demonstrated cryoprotection and result in cellular recoveries similar to DMSO. 17,18 Evidence from several groups indicates that the use of multiple cryoprotectants from the different families above, such as trehalose and proline, 16 or trehalose and glycerol, 19 exhibit improved cellular survival compared with either cryopreservative alone, suggesting that additive 13 or synergistic stabilizing effects are possible when multiple cryopreservatives are used.…”