• Bulletin of the Korean Chemical Society
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• v.25 no.4
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• pp.553-556
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• 2004

In this study we have performed ab initio computer simulations to investigate the conformational characteristics of the tetraethyl (1) and triethyl ester (2) of p-tert-butylcalix[4]arene. The structures of different conformational isomers for each compound have been optimized using ab initio RHF/6-31G methods. After optimization, B3LYP/6-31+G(d,p) single point calculations of the final structures are done to include the effect of electron correlation and the basis set with diffuse function and polarization function. Relative stability of tetraethyl ester (1) of p-tert-butylcalix[4]arene is in following order: cone (most stable) > partial cone > 1,3- alternate > 1,2-alternate isomer. Relative stability of triethyl ester (2) of p-tert-butylcalix[4]arene is in following order: cone (most stable) > 2-partial cone > 1-partial cone > 3-partial cone ~ 1,3-alternate ~ 1,2- alternate isomer.

• Bulletin of the Korean Chemical Society
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• v.25 no.12
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• pp.1911-1916
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• 2004

The conformational preference of tetrahomodioxacalix[4]arenes with three different para substituents on the phenolic ring has been investigated by using ab initio molecular orbital theory (RHF/6-31$G^{\ast}$) and density functional theory (B3LYP/6-31$G^{\ast}$). The stability order is predicted to be cone > C-1,2-alternate > partial cone > 1,3-alternate > COC-1,2-alternate. The distorted cone conformation is found to be most stable in a gas phase and the calculated results are in agreement with the reported $^1$H NMR and X-ray experimental observations. The substitution of methylene with dimethyleneoxa bridges increases the size of the annulus of the molecule, its conformational mobility, and the number of hydrogen bonding patterns. The thermodynamic stability and the conformational characteristics of tetrahomodioxacalix[4]arenes are discussed in regards of the number of phenolic hydrogen bonding patterns and the polarity of a molecule. The substituent effects on the para position of the phenolic ring are also introduced.

• Bulletin of the Korean Chemical Society
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• v.30 no.2
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• pp.423-428
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• 2009

The comparative study of three calix[4]heterocycles (calix[4]pyrrole, calix[4]furan, and calix[4]thiophene) has been theoretically performed by using high-level density functional theory (DFT) at the MPWB1K/6-311G$^{**}$//B3LYP/6- 311G$^{**}$ level. The effect of different hetero-atoms (nitrogen, oxygen, and sulfur) placed in the heterocycles on the conformational flexibility, thermodynamic stability order, cavity sizes, charge distributions, and binding propensities are examined. The thermodynamic stability differences between the conformers are found to be much greater in calix[4]pyrrole compared to those in calix[4]furan and calix[4]thiophene. Relatively larger NH group and higher dipole of a pyrrole ring in calix[4]pyrrole contribute to the higher energy barrier for the conformational conversions and relatively rigid potential energy surface compared to the case of calix[4]furan and calix[4]thiophene. The computational results herein provide theoretical understanding of the conformational flexibility and the thermodynamic nature which can be applied to understand the complexation behavior of the three calix[4]heterocycles.

• Proceedings of the Korean Biophysical Society Conference
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• 1997.07a
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• pp.39-39
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• 1997

Native strain of inhibitory SERPINS (Serine protease inhibitors) is thought to be used in the facile conformational switch to play biological regulation. Many heat stable variants of $\alpha$$_1$-antitrypsin, a prototype of inhibitory serpins, increased their stability by reducing the native strain.(omitted)

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2001.11b
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• pp.3-6
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• 2001

In common globular proteins, the native form is in its most stable state. However, the native form of inhibitory serpins (serine protease inhibitors) and some viral membrane fusion proteins is in a metastable state. Metastability in these proteins is critical to their biological functions. Our previous studies revealed that unusual interactions, such as side-chain overpacking, buried polar groups, surface hydrophobic pockets, and internal cavities are the structural basis of the native metastability. To understand the mechanism by which these structural defects regulate protein functions, cavity-filling mutations of a 1-antitrypsin, a prototype serpin, were characterized. Increasing conformational stability is correlated with decreasing inhibitory activity. Moreover, the activity loss appears to correlate with the decrease in the rate of the conformational switch during complex formation with a target protease. We also increased the stability of a 1-antitrypsin greatly via combining various stabilizing single amino acid substitutions that were distributed throughout the molecule. The results showed that a substantial increase of stability, over 13 kcal/mol, affected the inhibitory activity with a correlation of 11% activity loss per kcal/mol. The results strongly suggest that the native metastability of proteins is indeed a structural design that regulates protein functions and that the native strain of a 1-antitrypsin distributed throughout the molecule regulates the inhibitory function in a concerted manner.

• Electrical & Electronic Materials
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• v.14 no.12
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• pp.3-6
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• 2001

In common globular proteins, the native form is n its most stable state. However, the native form of inhibitory serpins (serine protease inhibitors) and some viral membrane fusion proteins is in a metastable state. Metastability in these proteins is critical to their biological functions. Our previous studies revealed that unusual interactions, such as side-chain overpacking, buried polar groups, surface hydrophobic pockets, ad internal cavities are the structural basis of the native metastability. To understand the mechanism by which these structural defects regulate protein functions, cavity-filling mutations of $\alpha$1-antitrypsin, a prototype serpin, were characterized. Increasing conformational stability is correlated with decreasing inhibitory activity. Moreover, the activity loss appears to correlate with the decrease in the rate of the conformational switch during complex formation with a target protease. We also increased the stability of $\alpha$1-antitrypsin greatly via combining various stabilizing single amino acid substitutions that were distributed throughout the molecule. The results showed that a substantial increase of stability, over 13 kcal/mol, affected the inhibitory activity with a correlation of 11% activity loss per kcal/mol. The results strongly suggest that the native metastability of proteins is indeed a structural design that regulates protein functions and that the native strain of $\alpha$1-antitrypsin distributed throughout the molecule regulates the inhibitory function in a concerted manner.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2001.11a
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• pp.3-6
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• 2001

In common globular proteins, the native form is in its most stable state. However, the native form of inhibitory serpins (serine protease inhibitors) and some viral membrane fusion proteins is in a metastable state. Metastability in these Proteins is critical to their biological functions. Our previous studies revealed that unusual interactions, such as side-chain overpacking, buried polar groups, surface hydrophobic pockets, and internal cavities are the structural basis of the native metastability. To understand the mechanism by which these structural defects regulate protein functions, cavity-filling mutations of ${\alpha}$1-antitrypsin, a prototype serpin, were characterized. Increasing conformational stability is correlated with decreasing inhibitory activity. Moreover, the activity loss appears to correlate with the decrease in the rate of the conformational switch during complex formation with a target protease. We also increased the stability of ${\alpha}$1-antitrypsin greatly via combining various stabilizing single amino acid substitutions that were distributed throughout the molecule. The results showed that a substantial increase of stability, over 13 kcal/mol, affected the inhibitory activity with a correlation of 11% activity loss per kcal/mol. The results strongly suggest that the native metastability of proteins is indeed a structural design that regulates protein functions and that the native strain of e 1-antitrypsin distributed throughout the molecule regulates the inhibitory function in a concerted manner.

• BMB Reports
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• v.40 no.2
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• pp.205-211
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• 2007

The stability curve - a plot of the Gibbs free energy of unfolding versus temperature - is calculated for bovine erythrocyte carbonic anhydrase in 150 mM sodium phosphate (pH = 7.0) from a combination of reversible differential scanning calorimetry measurements and isothermal guanidine hydrochloride titrations. The enzyme possesses two stable folded conformers with the conformational transition occurring at ~30$^{\circ}C$. The methodology yields a stability curve for the complete unfolding of the enzyme below this temperature but only the partial unfolding, to the molten globule state, above it. The transition state thermodynamics for the low- to physiological-temperature conformational change are calculated from slow-scan-rate differential scanning calorimetry measurements where it is found that the free energy barrier for the conversion is 90 kJ/mole and the transition state possesses a substantial unfolding quality. The data therefore suggest that the x-ray structure may differ considerably from the physiological structure and that the two conformers are not readily interconverted.

• Korean Journal of Food Science and Technology
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• v.25 no.3
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• pp.277-281
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• 1993

To elucidate the conformational stability of proteins in colloidal food system, molecular properties of various proteins such as chemically modified ${\beta}-lactoglobulin$, bovine serum albumin (BSA) structural intermediates, and ${\beta}-casein$ under chaotropic conditions, were examined using circular dichroism, SS bond content, and hydrodynamic radius determination. As refolding time increases, BSA intermediates approach the conformation of native BSA. And succinylation made ${\beta}-lactoglobulin$ have more aperiodic structure by increasing net negative charge. Also, under chaotropic conditions, the conformation of P-casein was affected by hydrophobic interactions. This study clearly indicates that hydrophobic interactions and electrostatic interactions are major contributing factors in conformational stability of proteins.

• Bulletin of the Korean Chemical Society
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• v.4 no.3
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• pp.133-139
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• 1983

To understand the importance of Y-base adjacent to the anticodon stabilizing codon-anticodon interaction, a study has been undertaken for the model compound involving the interaction between Y-base and anticodon as well as the participation of water molecule by calculating the conformational free energy using an empirical potential function. We restrict our analysis to sites directly associated with Y-base by varying only the backbone torsion angles of Y-base. The hydration and $Mg^{+2}$ binding effects on the conformational stability of Y-base are calculated and discussed. The free Y-base is proved to be less stable than the hydrated one. The free energy change due to the hydration of Y-base amounts to -119.5 kcal/mole, in which the conformational energy change is -142.4 kcal/mole and the configurational entropy change is -76.9 e. u. It is found that the water molecules bound to Y-base and $Mg^{+2}$ contribute to the conformation of Y-base dominantly.