• Bulletin of the Korean Chemical Society
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• v.33 no.3
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• pp.828-832
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• 2012

We performed replica exchange molecular dynamics (REMD) simulations of the tripzip2 peptide (betahairpin) using the GB implicit and TI3P explicit solvation models. By comparing the resulting free energy surfaces of these two solvation model, we found that the GB solvation model produced a distorted free energy map, but the explicit solvation model yielded a reasonable free energy landscape with a precise location of the native structure in its global free energy minimum state. Our result showed that in particular, the GB solvation model failed to describe the tryptophan packing of trpzip2, leading to a distorted free energy landscape. When the GB solvation model is replaced with the explicit solvation model, the distortion of free energy shape disappears with the native-like structure in the lowest free energy minimum state and the experimentally observed tryptophan packing is precisely recovered. This finding indicates that the main source of this problem is due to artifact of the GB solvation model. Therefore, further efforts to refine this model are needed for better predictions of various aromatic side chain packing forms in proteins.

• Bulletin of the Korean Chemical Society
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• v.31 no.5
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• pp.1247-1251
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• 2010

We propose an improved solvent contact model to estimate the solvation free energies of amino acids from individual atomic contributions. The modification of the solvation model involves the optimization of three kinds of parameters in the solvation free energy function: atomic fragmental volume, maximum atomic occupancy, and atomic solvation parameters. All of these atomic parameters for 17 atom types are developed by the operation of a standard genetic algorithm in such a way to minimize the difference between experimental and calculated solvation free energies. The present solvation model is able to predict the experimental solvation free energies of amino acids with the squared correlation coefficients of 0.94 and 0.93 for the parameterization with Gaussian and screened Coulomb potential as the envelope functions, respectively. This result indicates that the improved solvent contact model with the newly developed atomic parameters would be a useful tool for the estimation of the molecular solvation free energy of a protein in aqueous solution.

• Bulletin of the Korean Chemical Society
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• v.24 no.12
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• pp.1742-1750
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• 2003

In order to characterize the hydrophobic parameters of N-acetyl amino acid amides in 1-octanol/water, a theoretical calculation was carried out using a solvation free energy density model. The hydrophobicity parameters of the molecules are obtained with the consideration of the solvation free energy over the solvent volume surrounding the solute, using a grid model. Our method can account for the solvent accessible surface area of the molecules according to conformational variations. Through a comparison of the hydrophobicity of our calculation and that of other experimental/theoretical works, the solvation free energy density model is proven to be a useful tool for the evaluation of the hydrophobicity of amino acids and peptides. In order to evaluate the solvation free energy density model as a method of calculating the activity of drugs using the hydrophobicity of its building blocks, the contracture of Bradykinin potentiating pentapeptide was also predicted from the hydrophobicity of each residue. The solvation free energy density model can be used to employ descriptors for the prediction of peptide activities in drug discovery, as well as to calculate the hydrophobicity of amino acids.

• Bulletin of the Korean Chemical Society
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• v.26 no.4
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• pp.589-593
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• 2005

The solvation free energy of proton in methanol was calculated by B3LYP flavor of density functional calculations in combination with the Poisson-Boltzmann continuum solvation model. In order to check the adequacy of the computation level, the free energies of clustering in the gas phase were compared with the experimental data. The solvents were taken into account in a hybrid manner, i.e. one to five molecules of methanol were explicitly considered while other solvent molecules were represented with an implicit solvation model.

• Proceeding of EDISON Challenge
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• 2015.03a
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• pp.70-75
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• 2015

Fasciclin 1 (FAS1) is an extracellular protein whose aggregation in cornea leads to visual impairment. While a number of FAS1 mutants have been studied that exhibit enhanced/decreased aggregation propensity, no structural information has been provided so far that is associated with distinct aggregation potential. In this study, we have investigated the structural and thermodynamic characteristics of the wild-type FAS1 and its two mutants, R555Q and R555W, by using molecular dynamics simulations and three-dimensional reference interaction site model (3D-RISM) theory. We find that the hydrophobic solvent accessible surface area increases due to hydrophobic core repacking in the C-terminus caused by the mutation. We also find that the solvation free energy of the mutants increases due to the enhanced non-native H-bonding. These structural and thermodynamic changes upon mutation contribute to understand the aggregation of these mutants.

• Bulletin of the Korean Chemical Society
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• v.21 no.5
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• pp.503-509
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• 2000

The solvent effects on the relative free energies of solvation and the difference in partition coefficients (log P) for $Rb^+$ to $K^+$ mutation in several solvents have been investigated using Monte Carlo simulation (MCS) of statistical perturbation theory(SPT). In comparing the relative free energies for interconversion of one ion pair, $Rb^+$ to $K^+$, in $H_2O$(TIP4P) in this study with the relative free energies of the computer simulations and the experimental, we found that the figure in this study with the relative free energies of the computert simulations and the experimental, we found that the figure in this study is $-5.00\pm0.11$ kcal/mol and those of the computer simulations are $-5.40\pm1.9$, -5.5, and -5.4 kcal/mol. The experimental is -5.1 kcal/mol. There is good agreement among various studies, taking into account both methods used to obtain the hydration free energies and standard deviations. There is also good agreement between the calculated structural properties of this study and the simulations, ab initio and the experimental results. We have explained the deviation of the relationship between the free energy difference and the Onsager dielectric function of solvents by the electron pair donor properties of the solvents. For the $Rb^+$ and $K^+$ ion pair, the Onsager dielectric function of solvents (or solvent permittivity), donor number of solvent and the differences in solvation dominate the differences in the relative free energies of solvation and partition coefficients.

• Bulletin of the Korean Chemical Society
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• v.32 no.6
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• pp.1985-1992
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• 2011

The stable conformers of glycine and the inter-conversions between them were studied theoretically at various levels of theory, B3LYP, MP2, CCSD and CCSD(T), in the gas phase and in aqueous solution. In aqueous solution, the structures examined by use of the conductor-like polarizable continuum model (CPCM) with various cavity models, UA0, UAHF, UAKS, UFF, BONDI and PAULING, and by use of a discrete/continuum solvation model with eight water clusters. The Gibbs free energy differences between the neutral (NE) and zwitterionic conformers (ZW), ${\Delta}G_{Z-N}[=G_{ZW}-G_{NE}]$, in aqueous solution were well reproduced by using the BONDI and PAULING cavity models. However the ${\Delta}G_{Z-N}$ values were underestimated in other cavity models, although the ZW conformers existed as stable species in aqueous solution. In the studies of a discrete/continuum solvation model with eight water clusters, gas phase results are still insufficient to reproduce the experimental findings. However the ${\Delta}G_{Z-N}$ values calculated by use of CPCM method in aqueous solution agreed well with the experimental ones.

• Bulletin of the Korean Chemical Society
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• v.11 no.4
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• pp.309-313
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• 1990

The rates of solvolysis of trans-$[Co(N-eten)_2Cl_2)$+ (N-eten; N-ethylethylenediamine) have been investigated using spectrophotometric method in binary aqueous mixtures containing methyl alcohol, isopropyl alcohol, t-butyl alcohol, ethylene glycol and glycerol. The values of ${\Delta}H^{\neq}$ and ${\Delta}S^{\neq}$ obtained from temperature effect on the rate constants were $80{\sim}84 kJmol^{-1}$ and $- 28{\sim} - 45 JK^{-1}mol^{-1}.$ Extrema found in the variation of the enthalpy and entropy of activation with solvent composition correlated very well with extrema in the variation of the physical properties of mixture which relate to sharp change in the solvent structure. The reaction mechanism was discussed in terms of correlation diagrams involving the exess molar Gibbs function of mixing for the binary mixtures. The behavior of this cobalt(Ⅲ) complex was compared with that of t-butyl chloride. The application of free energy cycle to the process initial state to transition state in water and in the mixture showed that the solvation of transition state had dominant effect on the rates in the mixtures. It was found that $S_N1$ character was increased with increasing the content of co-solvent in the mixture.

• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3291-3296
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• 2010

A gelastatins (1), natural MMP inhibitors, and their hydroxamate analogues (2) in TACE enzyme evaluated for discovery of potent TACE inhibitors. We have employed molecular dynamics simulations to compute the relative free energy of hydration and binding to TACE for gelastatin (1) and its hydroxamate analogue (2). The relative free energy difference is directly described in this article using the free energy perturbation approach as a means to accurately predict the TACE inhibitor of gelastatin analogues. The results show that the good agreement between the experimental and theoretical relative free energies of binding, gelastatin hydroxamate (2) binds stronger to TACE by -3.37 kcal/mol. The desolvation energy costs significantly reduced binding affinity, hydroxamate group associated with high desolvation energy formed strong favorable interactions with TACE with more than compensated for the solvation costs and therefore led to an improvement in relative binding affinity.

• Proceeding of EDISON Challenge
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• 2015.03a
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• pp.151-155
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• 2015

The molecular interactions between the nucleic acid bases and water molecules are important in organism. Despite Adenine-Thymine Hoogsteen base pair and Guanine-Cytosine Watson-Crick base pair have been demonstrated to be most stable in a gas phase, the effect of water on the stability of these base pairs remains elusive. Here we report the structural and thermodynamic characteristics on possible Adenine-Thymine and Guanine-Cytosine base pairs in a gas phase as well as in an aqueous phase by using quantum mechanical method and statistical mechanical calculations. First, we optimized the direct base-pair interaction energies of four Adenine-Thymine base pairs (Hoogsteen base pair, reverse Hoogsteen base pair, Watson-Crick base pair, and reverse Watson-Crick base pair) and three Guanine-Cytosine base pairs (GC1 base pair, GC2 base pair, and Watson Crick base pair) in a gas phase at the $B3LYP/6-31+G^{**}$ level. Then, the effect of solvent was quantified by the electronic reorganization energy and the solvation free energy by statistical mechanical calculations. Thereby, we discuss the effect of water on the stability of Adenine-Thymine and Guanine-Cytosine base pairs, and argue why Adenine-Thymine Watson-Crick base pair and Guanine-Cytosine Watson-Crick base pair are most stable in an aqueous environment.