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

Conformation of ultra-long-chain fatty acid in lipid bilayer: Molecular dynamics study

Ultra-long-chain fatty acids (ULCFAs) are biosynthesized in the restricted tissues such as retina, testis, and skin. The conformation of a single ULCFA, in which the sn-1 unsaturated chain has 32 carbons, in three types of tensionless phospholipid bilayers is studied by molecular dynamics simulations. It is found that the ultra-long tail of the ULCFA flips between two leaflets and fluctuates among an elongation into the opposite leaflet, lying between two leaflets, and turning back. As the number ratio of lipids in the opposite leaflet increases, the ratio of the elongated shape linearly decreases in all three cases. Thus, ULCFAs can sense the density differences between the two leaflets and respond to these changes

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

Theoretical studies on electronic structure and properties of type I copper center in copper proteins

We present a cluster model representing type I copper (T1Cu) center of copperprotein, which corrsponds to Multicopper Oxidases, Azurin, Stelacyanin and so on. Theelectronic structure and physical properties such as molecular orbital, atomic partial charge,partial spin densities, ionization energy (IP) of reduced T1Cu, electron affinity (EA) of oxidizedT1Cu, the bond and the angle constants etc. are calculated by using two typicalDensity Functional Theory (DFT) functionals, which are B3LYP and M06, with 6-31G(d)basis set. We find the dependency of several properties such as atomic partial charge, partialspin densities, IP, and EA on the DFT functionals. We also find that the DFT functionals givea better contribution to bond constants, especially in case of the interaction between copperand the axial ligand. We calculate the maximum absorption wavelength of T1Cu center andfind relatively a good agreement with experimental data

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

Molecular dynamics study of free energy profile for dissociation of ligand from CA I active site

We investigate the binding/dissociation process of ligand molecule from carbonicanhydrase (CA) I carbonic anhydrase (CA) I enzyme by using all-atom moleculardynamics simulation. The force field parameters of zinc ion in the CA I active site are estimatedby quantum chemical calculations and are summarized in this paper. The free energyprofile for binding/dissociation process of ligand from CA I active site is calculated by thethermodynamic integration combined with the all-atom molecular dynamics simulation. Thebinding free energy as a function of the distance between the center of mass positions of CAI active site and the ligand molecule is estimated. The radial distribution function of theCA I-ligand complex is calculated from the trajectory of all-atom molecular dynamics (MD)simulation. We estimate the free energy surface from the radial distribution function. Wecan obtain the bond constant of the equilibrium state from the value of the free energy surface.We discuss the binding/dissociation process of ligand molecule by calculating the freeenergy profile to know the stability of the CA I-ligand complex with some thermodynamicproperties such as the binding free energy, the equilibrium state of the free energy surfaceand so on

Conformations of Three Types of Ultra-Long-Chain Fatty Acids in Multicomponent Lipid Bilayers

Ultra-long-chain fatty acids (ULCFAs) are biosynthesized in certain types of tissues, but their biological roles remain unknown. Here, we report how the conformation of ULCFAs depends on the length and unsaturated-bond ratio of the ultra-long chains and the composition of the host bilayer membrane using molecular dynamics simulations. The ultra-long chain of ULCFAs flips between the two leaflets and fluctuates among three conformations: elongated, L-shaped, and turned. Furthermore, we found that the saturated ultra-long chain exhibited an elongated conformation more frequently than the unsaturated chain. In addition, the truncation of the ultra-long chain at C26 had little effect on the remaining ULCFAs. ULCFAs respond to lipid-density differences in the two leaflets, and the ratio of the elongated and turned conformations changed to reduce this difference. However, in cholesterol-containing membranes, ULCFAs exhibit no density difference after the flip–flop of cholesterol removes the difference