• Bulletin of the Korean Chemical Society
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• v.12 no.5
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• pp.495-499
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• 1991

The changes in the free energy and hydration free energy of N-acetyl-N'-methylalaninamide in the unhydrated and hydrated states were calculated with ECEPP/2 and the hydration shell model. The configurational entropy change of each conformation in both states were computed by a harmonic method. To understand the hydration structure of each hydrated conformation, the hydration-shell coordination numbers of functional. groups of the molecule were estimated from water-accessible volumes, and the contributions of water-accessible volume and polarization of each group to the hydration free energy were analyzed. The results show a reasonable agreement with those of recent theoretical studies and experiments.

• Bulletin of the Korean Chemical Society
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• v.11 no.2
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• pp.144-149
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• 1990

Conformational free energy calculations using an empirical potential function (ECEPP/2) and the hydration shell model were carried out on the sulfonylurea herbicides of bensulfuron methyl (Londax) and metsulfuron methyl (Ally). The conformational energy was minimized from starting conformations which included possible combinations of torsion angles in the molecule. The conformational entropy of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecule in aqueous solution, the hydration free energy of each group was calculated and compared each other. It was found that the low-free-energy conformations of two molecules in aqueous solution prefer the overall folded structure, in which an interaction between the carbonyl group of ester in aryl ring and the first amido group of urea bridge plays an important role. From the analysis of total free energy, the hydration and conformational entropy are known to be essential in stabilizing low-free-energy conformations of Londax, whereas the conformational energy is proved to be a major contribution to the total free energy of low-free-energy conformations of Ally.

• Archives of Pharmacal Research
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• v.13 no.1
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• pp.43-50
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• 1990

Conformational free energy calculations using an empirical potential function (ECEPP/2) and hydration shell model were carried out on the four-4-aminodiphenyl sulfone analogues of 4, 4'-diamino-2' methyldiphenyl sulfone, 4, 2', 4-triaminodiphenyl sulfone, 4, 4'-diaminodiphenyl sulfone, and 4-aminodiphenyl sulfone as antibacterial agents on Mycobacterium lufu. The conformational energy was minimized from starting conformations which included possible combinations of torsion angles in the molecule. The conformational entropy change of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecule in aqueous solution, the contributions of water-accessible volume and the hydration free energy of each group or atom in the lowest-free-energy conformation was calculated and compared each other. From comparison of the computed lowest-free-energy conformations of four analogues with their antibacterial activities, it is known that the conformation and the hydrophobicity of sulfonyl group and its adjacent carbon atom in each compound are the essential factors to show the strong antibacterial activity.

• Bulletin of the Korean Chemical Society
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• v.14 no.2
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• pp.220-225
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• 1993

The influence of temperature and pressure on the free energy of the ion hydration has been considered. The ion radii measured by conductometric method and the saturated dielectric constant cited from other works were used to calculate the free energy in the hydration shell. The Born equation was modified in order to fit in our model. In our model, the environment of ion consists of three regions. The innermost one is the hydration shell in which water is immobilized and electrostricted, the middle one is the one which contains less ordered waters than the bulk medium, and the outermost one is the bulk water which is under the influence of the electric field of ion. Our results for the free energy of ion hydration were compared with those of other attempts. Especially, ${\Delta}$G$_{hyd}$ of $Li^+$ ion is considerably too negative in this study at given temperature, comparing with those of other attempts. But ${\Delta}$G$_{hyd}$ of other ions coincides with each other.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.329-336
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• 1995

Conformational free energy calculations using an empirical potential function and a hydration shell model(program CONBIO) were carried out on hypoglycemic agent acetohexamide and tolazamide in the unhydrated and hydrated states. The initial geometry of sulfonylureas was obtained from X-ray crystallographieal data and homologous molecular fragments. In both states, the feasible conformations were obtained from the calculations of conformational energy, conformational entropy, and hydration free energy by varying all the torsion angles of the molecules. From the calculation results, it is known that the conformations] entropy is the major contribution to stabflize the low-free-energy conformations of two sulfonylureas in both states. But, in hydrated state, the hydration does not directly affect each conformations. The intramolecular hydrogen bonding of sulfonylurea hydrogen and 7-membered nitrogen appeared to the conformations of tolazamide in both states. It is thought that the hydrogen bonding decrease steric hindrance on the receptor binding direction. The substitution of alicyclic or N-heterocyclic ring than that of carbons chain of urea moiety may be properly interaction between sulfonylureas and the putative pancreatic receptor.

• Proceeding of EDISON Challenge
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• 2014.03a
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• pp.103-113
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• 2014

Hydrophobicity is the key concept to understand the role of water in protein folding, protein self-assembly, and protein-ligand interaction. Conventionally, hydrophobicity of amino acids in a protein has been argued based on hydrophobicity scales determined for individual free amino acids, assuming that those scales are unaltered when amino acids are embedded in a protein. Here, we investigate how the hydrophobicity of constituent amino acids depends on the protein context, in particular, on the total charge and secondary structures of a protein. To this end, we compute and analyze the hydration free energy - free energy change upon hydration quantifying the hydrophobicity - of three short proteins based on the integral-equation theory of liquids. We find that the hydration free energy of charged amino acids is significantly affected by the protein total charge and exhibits contrasting behavior depending on the protein net charge being positive or negative. We also observe that amino acids in the central ${\beta}$-strand sandwiched by ${\beta}$-sheets display more enhanced hydrophobicity than free amino acids, whereas those in the ${\alpha}$-helix do not clearly show such a tendency. Our results provide novel insights into the hydrophobicity of amino acids, and will be valuable for rationalizing and predicting the strength of water-mediated interaction involved in the biological activity of proteins.

• YAKHAK HOEJI
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• v.36 no.6
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• pp.518-528
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• 1992

To determine the optimal conformation of sulfonylureas, the correlation between conformation and hypoglycemic activity of the two sulfonylureas of tolbutamide and chlorpropamide as hypoglycemic agent was studied using an empirical potential function (ECEPP/2) and the hydration shell model in the unhydrated and hydrated states. The conformational energy was minimized from several starting conformations with possible torsion angles in each molecule. The conformational entropy change of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecules in aqueous solution, the contribution of water-accessible volume of each group or atom in the lowest-free-energy conformation was calculated and compared each other. From comparison of the computed lowest-free-energy conformations of two sulfonylureas, it could be suggested that the hydration of sulfonylurea moiety is related to increase the hypoglycemic activity. From the calculation results, it was known that the conformational entropy is the major contribution to stabilize the low-free-energy conformations of two sulfonylureas in unhydrated state. Whereas, in hydrated state, the hydration free energy largely contributes to the total free energies of low-free-energy conformations of tolbutamide and conformational entropy contributes to stabilize the low-free-energy conformations of chlorpropamide. The torsion angles from phenyl ring to urea moiety of the low-free-energy conformations of the two sulfonylureas were shown the nearly regular trend. On the basis of these results, the conformation exhibiting the optimal hypoglycemic activity of sulfonylureas and the binding direction to pancreatic receptor site A could be predicted. Also, according to the side chain lengthening of urea moiety, tolbutamide showed various conformational change. Therefore, steric effect may be important factor in the interaction between sulfonylureas and the putative pancreatic receptor.

• YAKHAK HOEJI
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• v.33 no.6
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• pp.350-360
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• 1989

The conformation and activity of the four benzenesulfonyl analogues of 4-aminobenzene-sulfonamide, 4-aminobenzenesulfonic acid, 4-methylbenzenesulfonamide, and 4-methylbenzenesulfonic acid with antibacterial activity on Staphylococcus aureus were studied using an empirical potential function (ECEPP/2) and the hydration shell model. The conformational energies were minimized from the starting conformations which included possible combinations of torsion angles in each molecule. To understand the hydration effect on the conformation of the molecule in aqueous solution, the hydration free energy of each group was calculated and compared each other. The conformational entropies of low-free-energy coformation of benzenesulfonly analogues were computed by a harmonic approximation. From the correlation of lowest-free-energy conformation of each compound and its antibacterial activity, it was found that the hydration of sulfonyl groups and the substituents are the decisive factors to show antibacterial activities.

• Bulletin of the Korean Chemical Society
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• v.5 no.1
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• pp.27-32
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• 1984

To investigate the hydration effects on the conformational changes of N-pivaloly-L-prolyl-N-methyl-N'-isopropyl-L-alanin amide (PPMIA), the conformational free energy changes have been calculated by using an empirical potential function varying all the independent degrees of freedom of PPMIA backbones. It is found that cis conformers are folded by a strong intramolecular hydrogen bond involving both terminal CO and NH groups whereas trans conformers accommodate the open conformation. Conformers in the free state are proved to be less stable than in the hydrated state. The free energy changes of cis and trans PPMIA due to the hydration are -50.5 and -39.8 kcal/mole, their conformational energy changes are -52.3 and -41.0 kcal/mole, and their conformational entropy changes are -5.9 and -4.0 e.u., respectively. The free energy changes of cis PPMIA to trans PPMIA in the free and hydrated states are 5.3 and 16.0 kcal/mole, their conformational energy changes are 7.6 and 18.8 kcal/mole, and the entropy changes due to the conformational transitions correspond to 7.5 and 9.4 e.u., respectively. From these results, it is found that the bound water molecules play an important role in stabilizing the conformation of PPMIA.

• Proceeding of EDISON Challenge
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• 2016.03a
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• pp.163-166
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• 2016

Hydrophobicity is the key concept to understand the water plays in protein folding, protein aggregation, and protein-protein interaction. Traditionally, the hydrophobicity of protein is defined based on the scales of the hydrophobicity of residue, assuming that the hydrophobicity of free amino acids is maintained. Here, we explore how the hydrophobicity of constituting amino acids in protein rely on the protein context, in particular, on the total charge and secondary structures of a protein. To this end, we calculate and investigate the hydration free energy of three short proteins based on the integral-equation theory of liquids. We find that the hydration free energy of charged amino acids is significantly affected by the protein total charge and exhibits contrasting behavior depending on the protein total charge being positive or negative. We also observe that amino acids in the ${\beta}-sheets$ display more enhanced the hydrophobicity than amino acids in the loop, whereas those in the ${\alpha}-helix$ do not clearly show such a tendency. And the salt-bridge forming amino acids also exhibit increase of the hydrophobicity than that with no salt bridge. Our results provide novel insights into the hydrophobicity of amino acids, and will be valuable for rationalizing and predicting the strength of water-mediated interaction involved in the biological activity of proteins.