• Bulletin of the Korean Chemical Society
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• 제31권11호
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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.

• Bulletin of the Korean Chemical Society
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• 제31권10호
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• pp.2823-2829
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• 2010

We investigated the solvent effects on the relative free energies of binding of $Na^+$ and $Li^+$ ions to 12-crown-4 and ${\Delta}log\;K_s$ (the difference of stability constant of binding) by a Monte Carlo simulation of statistical perturbation theory (SPT) in several solvents. Comparing the relative free energies of binding of $Na^+$ and $Li^+$ ions to 12-crown-4, in $CH_3OH$ of this study with experimental works, there is a good agreement among the studies. We have reported the quantitative free energy polarity (of solvent) relationships (QFPR) of the relationship between the relative free energies and solvent polarity studied on the solvent effects on the relative free energies of binding of $Na^+$ and $Li^+$ ions to 12-crown-4.

• Bulletin of the Korean Chemical Society
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• 제20권7호
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• pp.815-818
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• 1999

The method of calculating the excess Helmholtz free energy from the averaged effective acceptance ratio for the Lennard-Jones fluid and the inverse twelve fluid has been slightly modified and applied to the two-center-Lennard-Jones liquid. The excess Helmholtz free energy is calculated directly from the average of the modified effective acceptance ratio through a single Metropolis Monte Carlo simulation. Therefore this method does not need any reference system. The results of the present method were satisfactory compared with those of the perturbation theories and the overlap ratio method.

• Bulletin of the Korean Chemical Society
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• 제21권12호
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• pp.1207-1212
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• 2000

The free energy simulation technique is used to evaluate the relative binding affinity of a set of hydroxyethylene isostere inhibitors of the HIV-1 protease. The binding reactions and an alchemical mutation construct the thermodynamic cycle, which reduces the free energy difference of the binding interactions into that of the alchemical processes. In the alchemical process, a methyl group is mutated into a hydrogen atom. Albeit the change is a small perturbation to the inhibitor-protease complex, it results in 25 fold difference in the binding constants. The simulation reproduces the experimentally measured binding affinities within 2% of the free energy difference. The protonation state of the catalytic aspartic acid residues is also investigated through the free energy simulations.

• Bulletin of the Korean Chemical Society
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• 제20권10호
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• pp.1129-1135
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• 1999

Free energy perturbation and molecular dynamics simulations were carried out to investigate the relative binding affinities of [17] ketonand (1) toward alkali metal cations in methanol. The binding affinities of 1 toward the alkali metal cations were calculated to be in the order Li+ > Na+ > K+ > Rb+ > Cs+, whereas our recent theoretically predicted and experimentally observed binding affinities for [18]starand (2) were in the order K+ > Rb+ > Cs+ > Na+ > Li+. The extremely different affinities of 1 and 2 toward smaller cations, Li + and Na+ , were explained in terms of the differences in their ability to change the conformation to accommodate cations of different sizes. The carbonyl groups constituting the central cavity of 1 can reorganize to form a cavity with the optimal M+ -O distance, even for the smallest Li+, without imposing serious strain on 1. The highest affinity of 1 for Li+ was predominantly due to the highest Coulombic attraction between the smallest Li+ and the carbonyl oxygens of 1.

• 소음진동
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• 제9권5호
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• pp.906-913
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• 1999

Time-dependent period and energy of free vibration of a string, whose length varies with time at a constant rate, are investigated by a traveling wave method. When the string length is increased, the vibration period increase, but the free vibration energy decrease with time. However, when the string undergoes retraction, the vibration energy increases with time. String tension together with non-zero instantaneous velocity at the moving boundary results in energy variation. Analytical solutions by the traveling wave method are compared with previous results using the perturbation method and Kotera's approach.

• Journal of Theoretical and Applied Mechanics
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• 제1권1호
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• pp.1-27
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• 1995

In this paper a finite element method for free-surface problems is described. the method is based on two different forms of Hamilton's principle. To test the present computational method two specific wave problems are investigated; the dispersion relations and the nonlinear effect for the well-known solitary waves are treated. The convergence test shows that the present scheme is more efficient than other existing methods, e.g. perturbation scheme.

• Bulletin of the Korean Chemical Society
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• 제29권2호
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• pp.363-371
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• 2008

As a computational method for the discovery of the effective agonists for PPARd, we address the usefulness of molecular dynamics free energy (MDFE) simulation with explicit solvent in terms of the accuracy and the computing cost. For this purpose, we establish an efficient computational protocol of thermodynamic integration (TI) that is superior to free energy perturbation (FEP) method in parallel computing environment. Using this protocol, the relative binding affinities of GW501516 and its derivatives for PPARd are calculated. The accuracy of our protocol was evaluated in two steps. First, we devise a thermodynamic cycle to calculate the absolute and relative hydration free energies of test molecules. This allows a self-consistent check for the accuracy of the calculation protocol. Second, the calculated relative binding affinities of the selected ligands are compared with experimental IC50 values. The average deviation of the calculated binding free energies from the experimental results amounts at the most to 1 kcal/mol. The computational efficiency of current protocol is also assessed by comparing its execution times with those of the sequential version of the TI protocol. The results show that the calculation can be accelerated by 4 times when compared to the sequential run. Based on the calculations with the parallel computational protocol, a new potential agonist of GW501516 derivative is proposed.

• Bulletin of the Korean Chemical Society
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• 제22권8호
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• pp.877-882
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• 2001

The solvent effects on the relative free energies of Eu3+ to Yb3+ ion mutation in solution have been investigated using a Monte Carlo simulation of statistical perturbation theory (SPT). Our results agree well with available data that were obtained by others. Particularly, the results of water (SPC/E) solvent are almost identical with experimental data. For the present Eu3+ and Yb3+ ions, the relative free energies of solvation vs. Born’s function of bulk solvents decrease with increasing Born’s function of bulk solvents. There is also good agreement between the calculated structural properties in this study and the published works obtained by computer simulation and experimental work.

• Bulletin of the Korean Chemical Society
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• 제21권5호
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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.