Desolvation Penalty for Burying Hydrogen-Bonded Peptide Groups in Protein Folding

Baldwin, Robert L.

doi:10.1021/jp107111f

Cited by 20 publications

(24 citation statements)

References 43 publications

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“…For example, the differences between the experimental and calculated solvation free energies for 1 and 2 in Figure 4 decrease from 4.8 and 4.3 kcal/mol in the previous solvation model to 0.2 and 0.1 kcal/mol in the present method, respectively, due to the inclusion of the self-solvation term and to the extension of atom types. This substantial improvement further exemplifies the importance of intramolecular interactions in the stabilization of organic molecules in solution, which was also proposed for the structural stability of proteins in solution [42]. …”

Section: Resultssupporting

confidence: 57%

“…The limited role of solvent molecules in the hydrogen-bond stabilization of solutes can be related with the fact that a strong hydrogen bond is more difficult to be established in solution than in the gas phase due to the role of rupturing or weakening the hydrogen bonds played by water molecules [42,43]. The extent of this negative solvent effect should be greater in the intermolecular solute-solvent hydrogen bond than in the intramolecular one because the former is exposed to bulk solvent in a larger part than the latter.…”

Section: Resultsmentioning

confidence: 99%

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New solvation free energy function comprising intermolecular solvation and intramolecular self-solvation terms

2013

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Solvation free energy is a fundamental thermodynamic quantity that should be determined to estimate various physicochemical properties of a molecule and the desolvation cost for its binding to macromolecular receptors. Here, we propose a new solvation free energy function through the improvement of the solvent-contact model, and test its applicability in estimating the solvation free energies of organic molecules with varying sizes and shapes. This new solvation free energy function is constructed by combining the existing solute-solvent interaction term with the self-solvation term that reflects the effects of intramolecular interactions on solvation. Four kinds of atomic parameters should be determined in this solvation model: atomic fragmental volume, maximum atomic occupancy, atomic solvation, and atomic self-solvation parameters. All of these parameters for total 37 atom types are optimized by the operation of a standard genetic algorithm in such a way to minimize the difference between the experimental solvation free energies and those calculated by the solvation free energy function for 362 organic molecules. The solvation free energies estimated from the new solvation model compare well with the experimental results with the associated squared correlation coefficients of 0.88 and 0.85 for training and test sets, respectively. The present solvation model is thus expected to be useful for estimating the solvation free energies of organic molecules.

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Section: Resultssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

New solvation free energy function comprising intermolecular solvation and intramolecular self-solvation terms

2013

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“…The value of (ΔCp/ASA) for protein unfolding is obtained as follows. The value of (ΔCp/n) from (19) is 13.9 ± 0.5 cal·K −1 ·mol −1 (see above), and the amount of nonpolar surface per residue exposed by unfolding is 42 Å 2 (23). The significant uncertainty in the latter number comes chiefly from uncertainty about how best to calculate the solvent-exposed nonpolar ASA in a completely unfolded protein.…”

Section: Analogy Between Protein Folding and Transfer Of An Alkane Somentioning

confidence: 99%

Properties of hydrophobic free energy found by gas–liquid transfer

Baldwin

2013

Proc. Natl. Acad. Sci. U.S.A.

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The hydrophobic free energy in current use is based on transfer of alkane solutes from liquid alkanes to water, and it has been argued recently that these values are incorrect and should be based instead on gas-liquid transfer data. Hydrophobic free energy is measured here by gas-liquid transfer of hydrocarbon gases from vapor to water. The new definition reduces more than twofold the values of the apparent hydrophobic free energy. Nevertheless, the newly defined hydrophobic free energy is still the dominant factor that drives protein folding as judged by ΔCp, the change in heat capacity, found from the free energy change for heat-induced protein unfolding. The ΔCp for protein unfolding agrees with ΔCp values for solvating hydrocarbon gases and disagrees with ΔCp for breaking peptide hydrogen bonds, which has the opposite sign. The ΔCp values for the enthalpy of liquid-liquid and gas-liquid transfer are similar. The plot of free energy against the apparent solvent-exposed surface area is given for linear alkanes, but only for a single conformation, the extended conformation, of these flexible-chain molecules. The ability of the gas-liquid hydrophobic factor to predict protein stability is tested and reasonable agreement is found, using published data for the dependences on temperature of the unfolding enthalpy of ribonuclease T1 and the solvation enthalpies of the nonpolar and polar groups.folding energetics | reference solvent | osmolytes | cavity work T he current method of measuring hydrophobic free energy is based on liquid-liquid transfer of alkane solutes and uses the solubility of liquid alkanes in water. The method was criticized by Ben-Naim and Marcus (1) because the solvation free energy of a nonpolar solute is found from gas-liquid transfer results. The original suggestion of Kauzmann (2) was to quantify hydrophobic free energy with data for the transfer of nonpolar solutes between water and a reference solvent. He drew an analogy between solvent transfer of a nonpolar solute and folding, which transfers nonpolar side chains out of water into the protein interior. It was pointed out recently (3) that, when the liquid-liquid transfer of an alkane solute is divided into two successive gas-liquid transfers, less than half of the overall transfer free energy occurs in the hydrophobic transfer from water into vapor, indicating that liquid-liquid transfer gives seriously incorrect values of hydrophobic free energy. Wolfenden and Lewis (4) showed earlier that the reason for a major free energy change when an alkane solute is transferred from vapor into liquid alkane is the presence of a strong interaction among alkane molecules in a liquid alkane.The conclusion drawn here is that hydrophobic free energy should be defined and measured by the hydrophobic transfer of alkane solutes from water into vapor. The consequences of making this change are examined. A pressing issue is whether hydrophobic free energy, whose apparent value is reduced more than twofold by changing from liquid-liquid to gas-liquid transfer,...

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“…However, if the desolvation of two potentially H‐bonding groups is not accompanied by H‐bond formation upon burial, the corresponding conformation will be penalized by the desolvation term. Considering the high polarity of water, the desolvation and electrostatic terms will typically be of comparable magnitudes . As a result, the formation of a buried H‐bond represents a minor (possibly negligible or even adverse) conformational driving force , but an important conformational steering force .…”

Section: Introductionmentioning

confidence: 99%

Solvent‐Modulated Influence of Intramolecular Hydrogen‐Bonding on the Conformational Properties of the Hydroxymethyl Group in Glucose and Galactose: A Molecular Dynamics Simulation Study

Lonardi

Oborský

Hünenberger

2016

Helvetica Chimica Acta

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Intramolecular hydrogen‐bonding (H‐bonding) is commonly regarded as a major determinant of the conformation of (bio)molecules. However, in an aqueous environment, solvent‐exposed H‐bonds are likely to represent only a marginal (possibly adverse) conformational driving as well as steering force. For example, the hydroxymethyl rotamers of glucose and galactose permitting the formation of an intramolecular H‐bond with the adjacent hydroxyl group are not favored in water but, in the opposite, least populated. This is because the solvent‐exposed H‐bond is dielectrically screened as well as subject to intense H‐bonding competition by the water molecules. In the present study, the effect of a decrease in the solvent polarity on this rotameric equilibrium is probed using molecular dynamics simulation. This is done by considering six physical solvents (H2O, DMSO, MeOH, CHCl3, CCl4, and vacuum), along with 19 artificial water‐like solvent models for which the dielectric permittivity and H‐bonding capacity can be modulated independently via a scaling of the O–H distance and of the atomic partial charges. In the high polarity solvents, the intramolecular H‐bond is observed, but arises as an opportunistic consequence of the proximity of the H‐bonding partners in a given rotameric state. Only when the polarity of the solvent is decreased does the intramolecular H‐bond start to induce a conformational pressure on the rotameric equilibrium. The artificial solvent series also reveals that the effects of the solvent permittivity and of its H‐bonding capacity mutually enhance each other, with a slightly larger influence of the permittivity. The hydroxymethyl conformation in hexopyranoses appears to be particularly sensitive to solvent‐polarity effects because the H‐bond involving the hydroxymethyl group is only one out of up to five H‐bonds capable of forming a network around the ring.

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Desolvation Penalty for Burying Hydrogen-Bonded Peptide Groups in Protein Folding

Cited by 20 publications

References 43 publications

New solvation free energy function comprising intermolecular solvation and intramolecular self-solvation terms

New solvation free energy function comprising intermolecular solvation and intramolecular self-solvation terms

Properties of hydrophobic free energy found by gas–liquid transfer

Solvent‐Modulated Influence of Intramolecular Hydrogen‐Bonding on the Conformational Properties of the Hydroxymethyl Group in Glucose and Galactose: A Molecular Dynamics Simulation Study

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