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Electrostatic Potential Maps (electrostatic + potential_map)
Selected AbstractsInvestigation of protein binding affinity and preferred orientations in ion exchange systems using a homologous protein libraryBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2009Wai Keen Chung Abstract A library of cold shock protein B (CspB) mutant variants was employed to study protein binding affinity and preferred orientations in cation exchange chromatography. Single site mutations introduced at charged amino acids on the protein surface resulted in a homologous protein set with varying charge density and distribution. The retention times of the mutants varied significantly during linear gradient chromatography. While the expected trends were observed with increasing or decreasing positive charge on the protein surface, the degree of change was a strong function of the location and microenvironment of the mutated amino acid. Quantitative structure,property relationship (QSPR) models were generated using a support vector regression technique that was able to give good predictions of the retention times of the various mutants. Molecular descriptors selected during model generation were used to elucidate the factors affecting protein retention. Electrostatic potential maps were also employed to provide insight into the effects of protein surface topography, charge density and charge distribution on protein binding affinity and possible preferred binding orientations. The use of this protein mutant library in concert with the qualitative and quantitative analyses presented in the article provides an improved understanding of protein behavior in ion exchange systems. Biotechnol. Bioeng. 2009; 102: 869,881. © 2008 Wiley Periodicals, Inc. [source] Identification of possible kinetically significant anion-binding sites in human serum transferrin using molecular modeling strategiesBIOPOLYMERS, Issue 2 2004Elizabeth Ambrose Amin Abstract Certain anions have been shown experimentally to influence the rate of iron release from human serum transferrin (HST), implying the existence of one or more allosteric kinetically significant anion- binding (KISAB) sites on or near the surface of the protein. A rank-ordered selection of potential HST KISAB sites has been obtained using a novel three-stage molecular modeling strategy. The crystal structure of HST (1A8E.pdb) was first subjected to a heuristic analysis, in which positively charged and hydrogen-bonding residues on or near the surface of the protein were identified. In this stage, a preliminary electrostatic potential map was also calculated, yielding six preliminary sites. Next, energy-grid calculations were conducted in order to identify anion,protein interaction energy minima, which resulted in the inclusion of three additional sites. Finally, three anions already shown experimentally to demonstrate varied effects on HST iron-release kinetics were placed at each potential site; molecular dynamics and molecular mechanics calculations were performed in order to elucidate the hydrogen-bonding environment around each anion of the protein as well as to calculate anion,protein-binding energies. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 205,215, 2004 [source] Ab initio Study of the Interactions between CO2 and N-Containing Organic HeterocyclesCHEMPHYSCHEM, Issue 2 2009Konstantinos D. Vogiatzis Abstract In the garden of dispersion: High-accuracy ab initio calculations are performed to determine the nature of the interactions and the most favorable geometries between CO2 and heteroaromatic molecules containing nitrogen (see figure). Dispersion forces play a key role in the stabilization of the dimer, because correlation effects represent about 50,% of the total interaction energy. The interactions between carbon dioxide and organic heterocyclic molecules containing nitrogen are studied by using high-accuracy ab initio methods. Various adsorption positions are examined for pyridine. The preferred configuration is an in-plane configuration. An electron donor,electron acceptor (EDA) mechanism between the carbon of CO2 and the nitrogen of the heterocycle and weak hydrogen bonds stabilize the complex, with important contributions from dispersion and induction forces. Quantitative results of the binding energy of CO2 to pyridine (C5H5N), pyrimidine, pyridazine, and pyrazine (C4H4N2), triazine (C3H3N3), imidazole (C3H4N2), tetrazole (CH2N4), purine (C5H4N4), imidazopyridine (C6H5N3), adenine (C5H5N5), and imidazopyridamine (C6H6N4) for the in-plane configuration are presented. For purine, three different binding sites are examined. An approximate coupled-cluster model including single and double excitations with a perturbative estimation of triple excitations (CCSD(T)) is used for benchmark calculations. The CCSD(T) basis-set limit is approximated from explicitly correlated second-order Møller,Plesset (MP2-F12) calculations in the aug-cc-pVTZ basis in conjunction with contributions from single, double, and triple excitations calculated at the CCSD(T)/6-311++G** level of theory. Extrapolations to the MP2 basis-set limit coincide with the MP2-F12 calculations. The results are interpreted in terms of electrostatic potential maps and electron density redistribution plots. The effectiveness of density functional theory with the empirical dispersion correction of Grimme (DFT-D) is also examined. [source] Manganese, Iron, Cobalt, and Nickel Oxo-, Peroxo-, and Superoxoclusters: A Density Functional Theory StudyCHEMPHYSCHEM, Issue 2 2004Ellie L. Uzunova Dr. Abstract The 3d-transition-metal dioxo-, peroxo-, and superoxoclusters with the general composition MO2, M(O2), and MOO (M=Mn, Fe, Co, and Ni) were studied by DFT by the B1LYP functional. The dioxides in their ground states represent the global minima for the M+O2 system. Both ground-state dioxides and the lowest-energy peroxides are in their (d-only) highest spin states. The 6A1 state of Co(O2) exceeds the d-only spin-multiplicity value (quartet), being nearly isoenergetic with the 4A1 state of Co(O2). The energy gain on transforming the peroxides to the corresponding dioxides decreases in the order Mn(O2)>Fe(O2)>Co(O2)>Ni(O2) and varies in the range 0.27,1.8 eV. The dissociation energy to M+O2 for all studied peroxides is less than 1 eV being the lowest (0.47 eV) for Mn(O2). The Mn and Fe peroxides need less than 0.3 eV to rupture one of the MO bonds to form the corresponding superoxide. Mn and Fe superoxides are less stable than the corresponding peroxides; the superoxide of Co is more stable than its peroxide, while Ni superoxide is unstable,its energy is above the limit of dissociation to Ni+O2. According to the electrostatic potential maps, the oxygen atoms in the peroxides are more nucleophilic than those in the dioxides and superoxides, in which the terminal oxygen atom is more nucleophilic than the M-bonded oxygen atom. This result differs from the expectations based on charge-distribution analysis. [source] Theoretical Prediction of the Phenoxyl Radical Formation Capacity and Cyclooxygenase Inhibition Relationships by Phenolic CompoundsMOLECULAR INFORMATICS, Issue 6 2002Juan Ruiz Abstract Due to the importance of the O-H bond dissociation in the antioxidant mechanism of anti-inflammatory phenols, we studied the biradical process Ph-OH,PhO.+H. for 25 phenolic compounds using ab initio calculations. Enthalpies of reaction (,Hr), changes in the electron density at the O-H bond critical point (,OH) and total atomic charges of ortho and para carbon atoms strongly correlate with the in vitro inhibition of cyclooxygenase activity by phenols. The most active compounds have large values of the electron density at the O-H bond (,OH), thus favouring the O-H bond dissociation. In contrast, inactive compounds have small values of the electron density at the O-H bond (,OH), thus reducing the hydrogen donation ability. These results are also supported by the representation of the molecular electrostatic potentials maps. The prediction of the cyclooxygenase inhibitory activity of the proposed QSAR equations is analysed using the multilineal (MLR) method. Finally, the differences in biological activity are examined by analysing the binding interactions of active compounds in the pocket site of human COX-2 enzyme structure derived from crystallographic X -ray data. [source] | ||||||||||