• Bulletin of the Korean Chemical Society
• /
• 제21권12호
• /
• pp.1207-1212
• /
• 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
• /
• 제31권11호
• /
• pp.3291-3296
• /
• 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
• /
• 제17권1호
• /
• pp.19-24
• /
• 1996

The potential energies of HIV-1 protease, inhibitor, and their complex have been calculated by molecular mechanics and the "binding energy", defined as the difference between the potential energy of complex and the sum of potential energies of HIV-1 protease and its inhibitor, has been compared to the free energy in inhibition reaction. The trend in these binding energies seems to agree with that in free energies.

• Bulletin of the Korean Chemical Society
• /
• 제29권2호
• /
• pp.363-371
• /
• 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
• /
• 제31권10호
• /
• pp.2823-2829
• /
• 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
• /
• 제35권6호
• /
• pp.1769-1776
• /
• 2014

Binding modes of a series of catechol derivatives such as protein tyrosine phosphatase 1B (PTP1B) inhibitors were identified by molecular modeling techniques. Docking, molecular dynamics simulations and free energy calculations were employed to determine the modes of these new inhibitors. Binding free energies were calculated by involving different energy components using the Molecular Mechanics-Poisson-Boltzmann Surface Area and Generalized Born Surface Area methods. Relatively larger binding energies were obtained for the catechol derivatives compared to one of the PTP1B inhibitors already in use. The Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) free energy decomposition analysis indicated that the hydroxyl functional groups and biphenyl ring system had favorable interactions with Met258, Tyr46, Gln262 and Phe182 residues of PTP1B. The results of hydrogen bound analysis indicated that catechol derivatives, in addition to hydrogen bonding interactions, Val49, Ile219, Gln266, Asp181 and amino acid residues of PTP1B are responsible for governing the inhibitor potency of the compounds. The information generated from the present study should be useful for the design of more potent PTP1B inhibitors as anti-diabetic agents.

• Bulletin of the Korean Chemical Society
• /
• 제32권spc8호
• /
• pp.3051-3056
• /
• 2011

We calculate the free energy surfaces for two small proteins and a protein-RNA complex system by using a lattice model approach. In particular, we employ the Munoz-Eaton model, which is a native-structure based statistical mechanical model for studying protein folding problem. The model can provide very useful insights into the folding mechanisms by allowing one to calculate the free energy surfaces efficiently. We first calculate the free energy surfaces of ubiquitin and BBL, using both approximate and recently developed exact solutions of the model. Ubiquitin exhibits a typical two-state folding behavior, while BBL downhill folding in our study. We then extend the method to study of a protein-RNA complex. In particular, we focus on PAZ-siRNA complex. In order to elucidate the interplay between folding and binding kinetics for this system we perform comparative studies of PAZ only, PAZ-siRNA complex and two mutated complexes. We find that folding and binding are strongly coupled with each other and the bound PAZ is more stable than the unbound PAZ. Our results also suggest that the binding sites of the siRNA may serve act as a nucleus in the folding process.

• Journal of Pharmaceutical Investigation
• /
• 제15권2호
• /
• pp.45-52
• /
• 1985

For the model tablets using mannitol and Avicel PH 101 as excipients, the patterns of disintegration and dissolution from the differences of physical properties were investigated. It was found that the patterns in the dissolution and binding forces in the interaction of materials by estimates of solid-solid or liquid surface free energy due to cohesive or adhesive properties of materials, and solid surface free energy in binding forces of tablet should be considered as an important factor in dissolution processes.

• 한국생물정보학회:학술대회논문집
• /
• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
• /
• pp.35-40
• /
• 2005

Interaction of twelve erythromycin A analogues with 50S ribosomal subunit were studied employing AutoDock 3.0.5. Results showed that all active macrolides bound at the same binding site with erythromycin A in contrast to the inactive analogues which bound at location slightly different than erythromycin A. The binding site showed consistency with the X-ray data from the perspectives of hydrogen bonding and hydrophobic interactions formed by erythromycins, roxithromycin, azithromycin, cethromycin and telithromycin with the ribosome. The inactive derivatives of erythromycin A anhydride showed higher binding free energy, while 5-desosaminyl erythronolides A and B even though having quiet similar values of binding free energy with the active analogues, docked at binding sites which are quiet different than the active analogues. These results suggest the molecular docking technique can be used in predicting the binding of erythromycin A analogues to their ribosomal target.

• 한국결정성장학회지
• /
• 제10권3호
• /
• pp.185-188
• /
• 2000

CdTe 단결정에서 중성 받게에 구속된 엑시톤 해리를 PL 스펙트럼의 온도의존성을 측정하여 조사하였다. 12 K에서 CdTe 단결정의 자유 엑시톤의 결합 에너지는 10 meV이고,중성받게에 구속된 결합 에너지는 7.17 meV 이며, 또 중성주게에 구속된 결합 에너지는 14 meV이였다. 또한 ($A^{\circ}$, X)의 활성화 에너지의 값으로부터($A^{\circ}$, X)의 해리는 자유 엑시톤에서 해리됨을 알 수 있었다.