Computation of Redox Potential of Molecule by Energy Representation Method

We have been applied the conventional approach based on the molecular dynamics simulation to estimate the redox potential so far. In this study, we have focused the computational conditions in order to estimate standard redox potential by using the energy representation method: we calculate excess chemical potential increasing the number of solvent molecules and sampling data for the preparation of energy distribution functions. From these results, we have found that the computational value of the standard redox potential is close to the experimental value in the case of the system with larger number of solvent molecules unaffected by the behavior of counter-ion when we take a sufficient sampling data for the energy distribution functions.Selected Papers from the International Symposium on Computational Science - International Symposium on Computational Science Kanazawa University, Japa

Structure and hydration free energy of ketone compound in neutral and cationic state by molecular dynamics simulation

Structure and hydration property of acetone and 3-pentaone in the neutral and cationic state were investigated by using molecular dynamics (MD) and free energy calculations. The force field parameters of stretching vibration, angle bending, and partial charges of each molecule in the neutral and cationic state were developed by using density functional theory (DFT) calculations with B3LYP method and 6-31+G** basis set. The optimized structures by using these force field parameters in gas phase were compared with the experimental data and AMBER force fields parameters (parm99). From the results, the optimized structure in the neutral state of acetone was in good agreement with the experimental data. The evaluated hydration free energy in the neutral state of acetone was closed to the experimental data, while that of 3-pentaone was little bit larger than the experimental data. The ionization effect of ketone molecule on the hydration free energies was found to be significant in both molecules

Computational Study of Oxidation Potential Fluctuation of Ketone Molecule

This study focus on investigating the oxidation potential fluctuation of organic molecule in the solution. The organic molecule that was investigated is 3-pentanone molecule that has oxi-dation potential 0.143 V experimentally. The oxidation potential was calculated using Born-Haber cycle approximation involving the calculation of gas phase Gibbs free energy and solvation energy of reduced and the oxidized state. The reduced state represents a neutral charge molecule and the oxidized state represents a radical cation molecule. The first, molecular dynamics (MD) simulation of both state was performed for 2 ns time. Then, 400 snapshot structures of both state molecule was captured. Gas phase Gibbs free energy and solvation energy were calculated using MP2 theory with cc-pvdz basis set and the solvation effect was approached using Polarizable Continuum Model (PCM). Normal Hydrogen Electrode (NHE), that has redox potential 4.44 V experimentally, was used as reference electrode. The result shows the different of gas phase Gibbs free energy average of both state was 756.97 ± 21.598 kJ/mol, and solvation energy average of reduced and oxidized state were -18.42 kJ/mol ± 1.482 kJ/mol, and -219.02 ± 1.094 kJ/mol respectively. Then, the oxidation potential was calculated by substituting gas phase Gibbs free energy and solvation energy into Born-Haber cycle approximation. The calculation result shows the average of oxidation po-tential value is 1.396 ± 0.225 V. The deviation of oxidation potential confirms the fluctuation of oxidation potential during the simulation

Binding Free Energy of Protein-Ligand by Combining Docking and MD Simulation: A Comparison of Calculation Methods

Accurate methods of computing the affinity of ligand with protein target are strongly needed in the drug discovery process. Many attempts have been made and several algorithms have been developed for this purpose. We compared the protein-ligand binding free energies (∆G) in various methods include docking score function, combining docking score function and molecular dynamics (MD) simulation with explicit and implicit solvent model, and molecular-mechanics Poisson Boltzmann surface area (MM-PBSA) approach with and without the inclusion of entropic contributions. We tested these various methods to human plasminogen kringle-3 domain protein with the ligand trans-(aminomethyl) cyclohexanecarboxylic acid (AMCHA). The results showed the comparison between these various methods and the experimental affinity value. We found that combining docking score function and MD simulation with explicit solvent model was more favorable and close to the experimental result. This indicated that combining docking score function and MD simulation with explicit solvent model could be more accurate and effective in the protein-ligand binding free energy calculation

Coarse-grained Simulation of Azurin Crystal Complex System: Protein–protein Interactions

Most of protein function analyses focus mainly on the physical properties of a sin-gle protein. Nevertheless, the environments where proteins perform their biological functions are crowded with macromolecules, such as lipid, nucleic acids, and other proteins. The interactions between macromolecules may be affected by molecular crowding. Therefore, as an initial step we here investigate the protein–protein interactions for gaining insights into molecular crowding effects on protein conformational changes. Computational molecular simulation is one of the useful and important tools to study the protein interactions. Here we develop a coarse-grained model and a topology-based potential interactions to simulate dynamical properties of multiprotein complex crys-tal structure. We apply them to simulate complex crystal structure of Pseudomonas Aeruginosa azurin, a small cupredoxin, which functions as an electron carrier in bacterial respiration. Since electron transfer on azurin plays an important role in the biological system, it is important to cha-racterize the protein interactions in azurin. In our simulation, the interactions between intra- and inter- domains are treated at the residue level with the implementation of the off lattice G¯o-like model. In each domain, bonded interactions between residues are described by bond stretching, bond angle bending, and torsional angle potentials. The non-bonded interactions, which are repre-sented by short range and long range potentials, describe the interactions both among residues and between proteins. We probe the protein–protein interactions by analyzing the protein binding. A simple clustering algorithm is applied to group the bound structures of protein complex. Moreover, we can investigate the importance of the long range interaction on the multiprotein complex system. These studies will serve as valuable insights for further investigation on molecular crowding effects

Theoretical study of a π-stacking interaction in carbonic anhydrase

Human carbonic anhydrase II (HCA II) catalyses the reversible hydration of CO2. In this enzyme, the imidazole ring of histidine at position 64 (His64) functions to transfer the productive proton from the zinc-bound water to the buffer molecule in bulk-water. X-ray data of HCA II show that His64 has two types of side chain orientations, ”in” and ”out”, representing the direction of the imidazole ring toward and away from the active site, respectively. Maupin et al. reported that the imidazole of His64 can be rotated in a model system of the active site to clarify the proton transfer of catalytic mechanism. However, the indole ring of tryptophan at position 5 (Trp5) that is located near the ”out” of the imidazole ring of His64 was not considered in the model system. In this study, in order to estimate detailed rotational properties of His64, we constructed two His64-containing models with and without Trp5, and then simulate the constructed structures by using MP2 method and 6-311++G(d,p) basis sets. This allows us to tentatively determine the potential energies of the π-stacking interaction of the imidazole with the indole in relation to the side chain rotation of His64. The result indicates that the π-stacking interaction causes an increase of the energy barrier between ”in” and ”out” conformations, implying that the rotational motion of His64 is not relevant to explain the proton transfer during catalysis. Alternatively, a steady position of His64 would be needed in the proton transfer in catalytic mechanism of HCA II

Prediction of Solvation Free Energy of Proteins: Molecular Dynamics Simulation and QSPR Model Approach

Solvation free energy has valuable role as represents the desolvation cost of a molecu-lar binding interaction, which is very important in a variety of chemical and biological processes. Therefore, many computational methods have been explored to predict this value. In this study, we attempted to find the correlation between experimental and calculated value of solvation free energy of proteins, containing organic molecules, by using quantitative structure property relation-ship (QSPR) model. To obtained a comparable value of solvation free energy which will be used as reference in QSPR model, we adopted energy representation (ER) method. And as this method works through molecular dynamic (MD) simulation, we then performed the MD simulation prior to the calculation by ER method. The results showed that the predicted solvation free energies were quite close to calculated values by ER method. We also found that the values of solvation free energy, both in MD simulation and ER method, were well correlated to solvent accessible surface area of hydrophobic portion.Selected Papers from the International Symposium on Computational Science - International Symposium on Computational Science Kanazawa University, Japa

Mikulicz ビョウ ノ チリョウ チュウ ニ カン ショウガイ デ ハッショウ シタ ジコ メンエキセイ スイエン ノ 1レイ

69 歳,女性.2004 年に他院耳鼻科にてシェーグレン症候群と診断され治療中であった.2010 年5月に肝機能障害を指摘されたために当科を受診した.初診時に両側上眼瞼の腫脹と両側耳下腺の腫大(約1 cm)を認めた.血液生化学検査では胆道系酵素の上昇を認め,またIgG は2308 mg/dl,IgG4 は498 mg/dl と高値を呈した.造影CT では膵はびまん性に腫大していた.内視鏡的逆行性膵胆管造影で膵管に特徴的な狭細像を認めたため自己免疫性膵炎と診断した.本症例の眼瞼腫脹と顎下腺腫脹は現在の診断基準ではMikulicz 病と診断が可能である.Mikulicz 病と自己免疫性膵炎の合併は少なくないものの,本邦における文献報告例は本例で11 例目である.A 69-year-old woman presented with a chief complaintof liver dysfunction in May 2010. Both palpebrae superiorand the parotid gland had been swollen for six years. Bloodtests showed increased levels of biliary system enzymesand serum IgG and IgG4. Enhanced computed tomographyrevealed a diffusely enlarged pancreas. A narrowed pancreaticduct revealed by endoscopic retrograde cholangio-pancreatographywas diagnosed as autoimmune pancreatitis.The swollen eyelid and enlarged submandibular gland indicateda diagnosis of Mikulicz\u27s disease. Case reports of Mikulicz\u27sdisease complicated with autoimmune pancreatitisare very rare

ショハツ カンサイボウ ガン ノ ビョウイン ト ヨゴ キテイ インシ ニ カン スル リンショウ テキ ケントウ

目的:初発肝細胞癌の病因と予後規定因子について検討し,2000年の我々の獨協医科大学病院症例を対象とした報告と比較することを目的とした.方法:初発肝細胞癌102例を対象とした.病因はB型肝炎 (HBV),C型肝炎 (HCV),NBNC,アルコールの4つに分類した.Kaplan-Meier法を用いて生存率を求め,Coxの比例ハザードモデルを用いて予後因子の検討を行った.得られた結果を2000年の報告と比較した.結果:病因はHBV 12.8%,HCV 60.7%,NBNC 15.7%,アルコール10.8%であり,HCVは減少し,NBNCとアルコールは増加傾向にあった.治療例の生存率は1年87.5%,2年78.0%,3年71.5%であり,近年の診断と治療の進歩による予後改善が確認された.腫瘍ステージがIII以上であること,およびPIVKA-II 40 mAU/ml以上の2つが独立した予後規定因子であった.結論:肝細胞癌の病因ではHCVが減少し,NBNCとアルコールが増加していた.腫瘍ステージ,PIVKA-IIが独立した生命予後規定因子であった.Purpose:The purpose of this study was to investigate the causes of initial hepatocellular carcinoma and the factors determining prognosis, and to compare the findings with those of our year 2000 report.Method:Subjects comprised 102 patients with initial hepatocellular carcinoma. Causes were divided into four categories: hepatitis B virus (HBV);hepatitis C virus (HCV);non-B, non-C hepatitis (NBNC);and alcohol. Survival rates were obtained using the Kaplan-Meier method and prognostic factors were investigated using Cox\u27s proportional hazards model. The results were compared with the findings of the year 2000 report.Results:The cause was HBV in 12.8 % of cases, HCV in 60.7%, NBNC in 15.7%, and alcohol in 10.8%. Frequency of HCV was decreased and frequencies of NBNC and alcohol showed increasing tendencies. The survival rate of treated patients was 87.5 % at 1 year, 78.0 % at 2 years, and 71.5 % at 3 years. Improved prognosis was confirmed with diagnosis in recent years and treatment advances. Two factors were independently associated with poor prognosis:tumor stage III or IV; and PIVKA-II level>40 mAU/ml.Conclusion:HCV decreased and NBNC and alcohol increased as causes of hepatocellular carcinoma. Factors independently associated with life prognosis were tumor stage and PIVKA-II level