Methanol Strengthens Hydrogen Bonds and Weakens Hydrophobic Interactions in Proteins – A Combined Molecular Dynamics and NMR study

Hwang, Soyoun; Shao, Qiang; Williams, Howard J.; Hilty, Christian; Gao, Yi Qin

doi:10.1021/jp111448a

Cited by 81 publications

(70 citation statements)

References 34 publications

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“…Water always seeks to form additional H-bonds, e.g., with any exposed protein amide units; hence, decreasing the protein-water H-bonding interaction strength is expected to strengthen the intra-protein H-bonds, as observed in a recent MD simulation, 91 and consequently increasing the stability of the folded state. In addition, our results are in agreement with several previous studies.…”

Section: Resultsmentioning

confidence: 88%

Solute’s Perspective on How Trimethylamine Oxide, Urea, and Guanidine Hydrochloride Affect Water’s Hydrogen Bonding Ability

Pazos

Gai

2012

J. Phys. Chem. B

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While the thermodynamic effects of trimethylamine oxide (TMAO), urea and guanidine hydrochloride (GdnHCl) on protein stability are well understood, the underlying mechanisms of action are less well characterized and, in some cases, even under debate. Herein, we employ the stretching vibration of two infrared (IR) reporters, i.e., nitrile (C≡N) and carbonyl (C=O), to directly probe how these cosolvents mediate the ability of water to form hydrogen bonds with the solute of interest, e.g., a peptide. Our results show that these three agents, despite having different effects on protein stability, all act to decrease the strength of the hydrogen bonds formed between water and the infrared probe. While the behavior of TMAO appears to be consistent with its protein-protecting ability, those of urea and GdnHCl are inconsistent with their role as protein denaturants. The latter is of particular interest as it provides strong evidence indicating that although urea and GdnHCl can perturb the hydrogen-bonding property of water, their protein-denaturing ability does not arise from a simple indirect mechanism.

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Section: Resultsmentioning

confidence: 88%

Solute’s Perspective on How Trimethylamine Oxide, Urea, and Guanidine Hydrochloride Affect Water’s Hydrogen Bonding Ability

Pazos

Gai

2012

J. Phys. Chem. B

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“…The average RMSD value of about 9.0 ± 1.7 Å predicted for the β-component is significantly larger than the experimental value of only 3.1 ± 1.0 Å [16]. This large difference between calculated and experimental RMSD values of the Lchβ peptide can be most likely attributed to solvent effects since, the NMR experiments were performed in methanol solution which is know to stabilize secondary structure elements [18]. …”

Section: Resultsmentioning

confidence: 99%

“…This is particularly true for the Lchα, for which a root-mean-square deviation of the atomic positions of 6.45 ± 1.79 Å has been estimated. [16] Furthermore, since the NMR experiments were performed in methanol which is known to enhance secondary structure formation [18], the structural properties of these peptides in aqueous solution remain unsolved.…”

Section: Introductionmentioning

confidence: 99%

Structure, dynamics and kinetics of two-component Lantibiotic Lichenicidin

et al. 2017

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Two variants of the two-component Lantibiotic Lichenicidin, produced by the strains B. Licheniformis VK21 and I89 (Lchα/ Lchβ and Bliα/ Bliβ peptides, respectively) have been investigated by means of 2 μs-long all-atom molecular dynamics simulations combined with Markov State Models. This rigorous statistical analysis enabled to evaluate the dynamic and kinetic properties of the aforementioned systems which are not accessible via experimental techniques. The structural flexibility characteristic of these small peptides is understood by a delicate equilibrium between random coil, α-helices and β-sheet structures. The undergoing secondary structure transitions from an α-helix to a β-sheet observed for Lchα and Lchβ peptides, were not present in the Bliα component and provide new insights to understand their mechanism of action.

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“…The hydrophobic and hydrophilic properties of the organic solvent in a protein environment as well as exposed surface residues of the protein govern the type of interactions that are formed between protein and solvent molecules (Patargias, Harris & Harding, 2010). Previous results from MD simulations have also elaborated on how methanol strengthens hydrogen bonding and weakens hydrophobic interactions in proteins (Hwang et al, 2011). …”

Section: Resultsmentioning

confidence: 99%

Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

Maiangwa

Ali

Salleh

et al. 2017

PeerJ

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The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD) of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol) and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA) for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent systems, which could lead to weaknesses in the catalytic H-bond network and most likely a drop in catalytic activity. The conformational variation of the lid domain caused by the solvent molecules influenced its gradual opening. Formation of additional hydrogen bonds and hydrophobic interactions indicates that the contribution of the cooperative network of interactions could retain the stability of the protein in some solvent systems. Time-correlated atomic motions were used to characterize the correlations between the motions of the atoms from atomic coordinates. The resulting cross-correlation map revealed that the organic solvent mixtures performed functional, concerted, correlated motions in regions of residues of the lid domain to other residues. These observations suggest that varying lengths of polar organic solvents play a significant role in introducing dynamic conformational diversity in proteins in a decreasing order of polarity.

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Methanol Strengthens Hydrogen Bonds and Weakens Hydrophobic Interactions in Proteins – A Combined Molecular Dynamics and NMR study

Cited by 81 publications

References 34 publications

Solute’s Perspective on How Trimethylamine Oxide, Urea, and Guanidine Hydrochloride Affect Water’s Hydrogen Bonding Ability

Solute’s Perspective on How Trimethylamine Oxide, Urea, and Guanidine Hydrochloride Affect Water’s Hydrogen Bonding Ability

Structure, dynamics and kinetics of two-component Lantibiotic Lichenicidin

Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

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