Characterization of Experimentally Determined Native-Structure Models of a Protein Using Energetic and Entropic Components of Free-Energy Function

Mishima, Hirokazu; Yasuda, Satoshi; Yoshidome, Takashi; Oshima, Hiraku; Harano, Yuichi; Ikeguchi, Mitsunori; Kinoshita, Masahiro

doi:10.1021/jp301541z

Cited by 7 publications

(9 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The procedure of calculating S V of a protein with a prescribed structure comprises the following four steps (Mishima et al 2012).…”

Section: Hybrid Of Integral Equation Theory and Morphometric Approachmentioning

confidence: 99%

“…The high reliability of our hybrid method in calculating S V has been demonstrated in the following examples: quantitative reproduction of the experimentally measured changes in thermodynamic quantities upon apoPC folding; elucidation of the molecular mechanisms of pressure (Harano et al 2008;Yoshidome et al 2009) and cold (Oshima et al 2009; denaturating of proteins; proposal of a reliable measure of the thermal stability of proteins ; structural stability of membrane proteins ); development of a free-energy function capturing the features of the native fold for discriminating it from a number of misfolded decoys ); development of a reliable method of characterizing the native-structure models of a protein determined through the X-ray crystallography and NMR experiments combined with structure calculations (Mishima et al 2012); and prediction of the so-called hot spots (i.e., residues accounting for the majority of the protein-protein binding free energy despite that they comprise only a small fraction of the protein-protein interface) in protein-protein complexes .…”

Section: Hybrid Of Integral Equation Theory and Morphometric Approachmentioning

confidence: 99%

See 1 more Smart Citation

A new theoretical approach to biological self-assembly

Kinoshita

2013

Biophys Rev

Self Cite

View full text Add to dashboard Cite

Upon biological self-assembly, the number of accessible translational configurations of water in the system increases considerably, leading to a large gain in water entropy. It is important to calculate the solvation entropy of a biomolecule with a prescribed structure by accounting for the change in water-water correlations caused by solute insertion. Modeling water as a dielectric continuum is not capable of capturing the physical essence of the water entropy effect. As a reliable tool, we propose a hybrid of the angle-dependent integral equation theory combined with a multipolar water model and a morphometric approach. Using our methods wherein the water entropy effect is treated as the key factor, we can elucidate a variety of processes such as protein folding, cold, pressure, and heat denaturating of a protein, molecular recognition, ordered association of proteins such as amyloid fibril formation, and functioning of ATP-driven proteins.

show abstract

“…The procedure of calculating S V of a protein with a prescribed structure comprises the following four steps (Mishima et al 2012).…”

Section: Hybrid Of Integral Equation Theory and Morphometric Approachmentioning

confidence: 99%

Section: Hybrid Of Integral Equation Theory and Morphometric Approachmentioning

confidence: 99%

A new theoretical approach to biological self-assembly

Kinoshita

2013

Biophys Rev

Self Cite

View full text Add to dashboard Cite

show abstract

“…, S, and F are strongly dependent on the protein structure. The procedures of calculating the entropic component S/k B and the energetic component /(k B T 0 ) are briefly described below (more details are given in our earlier publications 3,4,15,36 ).…”

Section: B Free-energy Functionmentioning

confidence: 99%

“…Further, using F and its energetic and entropic components ( /(k B T 0 ) and S/k B , respectively) we have recently developed a reliable method of characterizing the NS models of a protein determined through the X-ray crystallography and NMR experiments combined with structure calculations. 36 The approximations employed in calculating , S, and F can thus be justified by these successful results.…”

Section: E Performance Of Free-energy Functionmentioning

confidence: 99%

Structural stability of proteins in aqueous and nonpolar environments

Yasuda

Oshima

Kinoshita

2012

The Journal of Chemical Physics

Self Cite

View full text Add to dashboard Cite

A protein folds into its native structure with the α-helix and∕or β-sheet in aqueous solution under the physiological condition. The relative content of these secondary structures largely varies from protein to protein. However, such structural variability is not exhibited in nonaqueous environment. For example, there is a strong trend that alcohol induces a protein to form α-helices, and many of the membrane proteins within the lipid bilayer consists of α-helices. Here we investigate the structural stability of proteins in aqueous and nonpolar environments using our recently developed free-energy function F = (Λ - TS)∕(k(B)T(0)) = Λ∕(k(B)T(0)) - S∕k(B) (T(0) = 298 K and the absolute temperature T is set at T(0)) which is based on statistical thermodynamics. Λ∕(k(B)T(0)) and S∕k(B) are the energetic and entropic components, respectively, and k(B) is Boltzmann's constant. A smaller value of the positive quantity, -S, represents higher efficiency of the backbone and side-chain packing promoted by the entropic effect arising from the translational displacement of solvent molecules or the CH(2), CH(3), and CH groups which constitute nonpolar chains of lipid molecules. As for Λ, in aqueous solution, a transition to a more compact structure of a protein accompanies the break of protein-solvent hydrogen bonds: As the number of donors and acceptors buried without protein intramolecular hydrogen bonding increases, Λ becomes higher. In nonpolar solvent, lower Λ simply implies more intramolecular hydrogen bonds formed. We find the following. The α-helix and β-sheet are advantageous with respect to -S as well as Λ and to be formed as much as possible. In aqueous solution, the solvent-entropy effect on the structural stability is so strong that the close packing of side chains is dominantly important, and the α-helix and β-sheet contents are judiciously adjusted to accomplish it. In nonpolar solvent, the solvent-entropy effect is substantially weaker than in aqueous solution. Λ is crucial and the α-helix is more stable than the β-sheet in terms of Λ, which develops a tendency that α-helices are exclusively chosen. For a membrane protein, α-helices are stabilized as fundamental structural units for the same reason, but their arrangement is performed through the entropic effect mentioned above.

show abstract

“…The NMR models are constructed by a structure calculation upon which the structural information experimentally obtained as a set of constraints is imposed. 43 Typical constraints are the nuclear Overhauser effect (NOE), residual dipolar coupling (RDC), hydrogen bonding, and dihedral angle restraints. Unless the amount of constraints is sufficiently large, the models constructed are substantially influenced by the structure calculation employed.…”

Section: E Proteins and Mutations Consideredmentioning

confidence: 99%

On the physics of thermal-stability changes upon mutations of a protein

Murakami

Oshima

Hayashi

et al. 2015

The Journal of Chemical Physics

Self Cite

View full text Add to dashboard Cite

It is of great interest from both scientific and practical viewpoints to theoretically predict the thermal-stability changes upon mutations of a protein. However, such a prediction is an intricate task. Up to now, significantly many approaches for the prediction have been reported in the literature. They always include parameters which are adjusted so that the prediction results can be best fitted to the experimental data for a sufficiently large set of proteins and mutations. The inclusion is necessitated to achieve satisfactorily high prediction performance. A problem is that the resulting values of the parameters are often physically meaningless, and the physicochemical factors governing the thermal-stability changes upon mutations are rather ambiguous. Here, we develop a new measure of the thermal stability. Protein folding is accompanied by a large gain of water entropy (the entropic excluded-volume (EV) effect), loss of protein conformational entropy, and increase in enthalpy. The enthalpy increase originates primarily from the following: The energy increase due to the break of protein-water hydrogen bonds (HBs) upon folding cannot completely be cancelled out by the energy decrease brought by the formation of protein intramolecular HBs. We develop the measure on the basis of only these three factors and apply it to the prediction of the thermal-stability changes upon mutations. As a consequence, an approach toward the prediction is obtained. It is distinguished from the previously reported approaches in the following respects: The parameters adjusted in the manner mentioned above are not employed at all, and the entropic EV effect, which is ascribed to the translational displacement of water molecules coexisting with the protein in the system, is fully taken into account using a molecular model for water. Our approach is compared with one of the most popular approaches, FOLD-X, in terms of the prediction performance not only for single mutations but also for double, triple, and higher-fold (up to sevenfold) mutations. It is shown that on the whole our approach and FOLD-X exhibit almost the same performance despite that the latter uses the adjusting parameters. For multiple mutations, however, our approach is far superior to FOLD-X. Five multiple mutations for staphylococcal nuclease lead to highly enhanced stabilities, but we find that this high enhancement arises from the entropic EV effect. The neglect of this effect in FOLD-X is a principal reason for its ill success. A conclusion is that the three factors mentioned above play essential roles in elucidating the thermal-stability changes upon mutations.

show abstract

Characterization of Experimentally Determined Native-Structure Models of a Protein Using Energetic and Entropic Components of Free-Energy Function

Cited by 7 publications

References 55 publications

A new theoretical approach to biological self-assembly

A new theoretical approach to biological self-assembly

Structural stability of proteins in aqueous and nonpolar environments

On the physics of thermal-stability changes upon mutations of a protein

Contact Info

Product

Resources

About