Density functional calculations of 15N chemical shifts in solvated dipeptides

We performed density functional calculations to examine the effects of solvation, hydrogen bonding, backbone conformation, and the side chain on 15N chemical shielding in proteins. We used N-methylacetamide (NMA) and N-formyl-alanyl-X (with X being one of the 19 naturally occurring amino acids excluding proline) as model systems. In addition, calculations were performed for selected fragments from protein GB3. The conducting polarizable continuum model was employed to include the effect of solvent in the density functional calculations. Our calculations for NMA show that the augmentation of the polarizable continuum model with the explicit water molecules in the first solvation shell has a significant influence on isotropic 15N chemical shift but not as much on the chemical shift anisotropy. The difference in the isotropic chemical shift between the standard beta-sheet and alpha-helical conformations ranges from 0.8 to 6.2 ppm depending on the residue type, with the mean of 2.7 ppm. This is in good agreement with the experimental chemical shifts averaged over a database of 36 proteins containing >6100 amino acid residues. The orientation of the 15N chemical shielding tensor as well as its anisotropy and asymmetry are also in the range of values experimentally observed for peptides and proteins.     

Computational insight into complex structures of thorium coordination with N,N’- bis(3-allyl salicylidene)-o-phenylenediamine

Theoretical calculations on the structure of Th(IV) complex containing N, N’- bis(3-allyl salicylidene)-o-phenylenediamine (BASPDA) were performed using density functional theory (DFT) at the B3LYP/6-311G** level. The geometrical structural parameters and infrared spectra results of the Th(BASPDA)₂ from the calculation were compared with the parallel dislocated structure (PDS) obtained in laboratory. The calculated structural parameters were in good agreement with the experimental results. In addition, based on the calculations, a stereoisomer SFS (staggered finger “?+?” structure) of the Th(BASPDA)₂ complex was forecasted by the analysis of a comprehensive method. The charge distribution, structural parameters, bond order indices, spectral properties and thermodynamic properties as well as the molecular orbitals of the two possible crystal structures of Th(BASPDA)₂ were also systematically studied. It was expected that this work could provide insightful information for understanding the properties of Th (BASPDA)₂ complex at the molecular level.     

Comparison of three different ways of measuring distances between residences and high voltage power lines

The aim of this study was to evaluate whether distance data based on calculations by use of digitalized geographical information systems (GIS) and distance data based on measurements on 1:5000 maps agree sufficiently with on site distance measurements to be used as input to magnetic field calculations in epidemiological studies. The analysis were performed by use of weighted kappa (kappa(w)) statistical method described by Bland and Altman for comparison of measures of agreement. Map measurements showed better agreement with on site measurements than GIS calculations did. However, we consider both methods appropriate for use in larger epidemiological studies if the results are interpreted with caution. GIS calculations have the advantage of being both time and cost saving.     

Theoretical and experimental studies of vibrational spectra and thermodynamical analysis of 3�?bromopropiophenone and 4�?bromo-3-chloropropiophenone

Quantum chemical calculations of molecular geometries, vibrational wavenumbers and thermodynamical properties of 3'-bromopropiophenone and 4'-bromo-3-chloropropiophenone were carried out using Hartree-Fock (HF) and density functional theory (DFT) using hybrid functional B3LYP with 6-31?G (d,p) as basis set. The optimized geometrical parameters obtained by HF and DFT calculations are in good agreement with the experimental FTIR and FT Raman spectral datas. The observed and the calculated frequencies are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically constructed simulated spectrograms.     

Conformation and hydrogen ion titration of proteins: a continuum electrostatic model with conformational flexibility.

A new method for including local conformational flexibility in calculations of the hydrogen ion titration of proteins using macroscopic electrostatic models is presented. Intrinsic pKa values and electrostatic interactions between titrating sites are calculated from an ensemble of conformers in which the positions of titrating side chains are systematically varied. The method is applied to the Asp, Glu, and Tyr residues of hen lysozyme. The effects of different minimization and/or sampling protocols for both single-conformer and multi-conformer calculations are studied. For single-conformer calculations it is found that the results are sensitive to the choice of all-hydrogen versus polar-hydrogen-only atomic models and to the minimization protocol chosen. The best overall agreement of single-conformer calculations with experiment is obtained with an all-hydrogen model and either a two-step minimization process or minimization using a high dielectric constant. Multi-conformational calculations give significantly improved agreement with experiment, slightly smaller shifts between model compound pKa values and calculated intrinsic pKa values, and reduced sensitivity of the intrinsic pKa calculations to the initial details of the structure compared to single-conformer calculations. The extent of these improvements depends on the type of minimization used during the generation of conformers, with more extensive minimization giving greater improvements. The ordering of the titrations of the active-site residues, Glu-35 and Asp-52, is particularly sensitive to the minimization and sampling protocols used. The balance of strong site-site interactions in the active site suggests a need for including site-site conformational correlations.     

Density functional theory study of N-H...O, O-H...O and C-H...O hydrogen-bonding effects on the 14N and 2H nuclear quadrupole coupling tensors of N-acetyl-valine

Hydrogen-bonding effects in the crystalline structure of N-acetyl-valine, NAV, were studied using the (14)N and (2)H quadrupole coupling tensors via density functional theory. The calculations were carried out at the B3LYP level with the 6-311++G(d,p) and 6-311+G(d) basis sets. The theoretical quadrupole coupling components and their relative orientation in the molecular frame axes at the nitrogen site are compared to experimental values. This nucleus is involved in a rather strong intermolecular O=CNH...O=CNH hydrogen bond, r(N-H...O(1))=2.04 A and angleN-H...O(1)=171.53 degrees. A reasonably good agreement between the experimentally obtained (2)H quadrupole coupling tensors and the B3LYP/6-311++G(d,p) calculations is achievable only in molecular model where a complete hydrogen-bonding network is considered.     

Optical properties of P3HT and N2200 polymers: a performance study of an optimally tuned DFT functional

The optical properties of systems composed of the polymers PolyeraActivInk? N2200 and P3HT are experimentally and theoretically investigated using UV-Vis spectroscopy and time-dependent density functional theory calculations, respectively. From a theoretical point of view, we carried out an analysis considering several functionals and model oligomers of different sizes to mimic the polymers. As our studies were performed with and without solvents, a first important result regards the fact that, by considering solvent effects, a better agreement between theoretical and experimental results could be achieved. Our findings also show that an optimally tuned functional is better suited to describe the experimental absorption profile than a hybrid one for the flexible polymer (P3HT). For the almost rigid polymer considered here (N2200), on the other hand, hybrid functionals may perform better than tuned functionals.     

Continuum solvent model calculations of alamethicin-membrane interactions: thermodynamic aspects

Alamethicin is a 20-amino acid antibiotic peptide that forms voltage-gated ion channels in lipid bilayers. Here we report calculations of its association free energy with membranes. The calculations take into account the various free-energy terms that contribute to the transfer of the peptide from the aqueous phase into bilayers of different widths. The electrostatic and nonpolar contributions to the solvation free energy are calculated using continuum solvent models. The contributions from the lipid perturbation and membrane deformation effects and the entropy loss associated with peptide immobilization in the bilayer are estimated from a statistical thermodynamic model. The calculations were carried out using two classes of experimentally observed conformations, both of which are helical: the NMR and the x-ray crystal structures. Our calculations show that alamethicin is unlikely to partition into bilayers in any of the NMR conformations because they have uncompensated backbone hydrogen bonds and their association with the membrane involves a large electrostatic solvation free energy penalty. In contrast, the x-ray conformations provide enough backbone hydrogen bonds for the peptide to associate with bilayers. We tested numerous transmembrane and surface orientations of the peptide in bilayers, and our calculations indicate that the most favorable orientation is transmembrane, where the peptide protrudes approximately 4 A into the water-membrane interface, in very good agreement with electron paramagnetic resonance and oriented circular dichroism measurements. The calculations were carried out using two alamethicin isoforms: one with glutamine and the other with glutamate in the 18th position. The calculations indicate that the two isoforms have similar membrane orientations and that their insertion into the membrane is likely to involve a 2-A deformation of the bilayer, again, in good agreement with experimental data. The implications of the results for the biological function of alamethicin and its capacity to oligomerize and form ion channels are discussed.     

Density functional calculations of chemical shielding of backbone <Superscript>15</Superscript>N in helical residues of protein G

We performed density functional calculations of backbone ¹⁵N chemical shielding tensors in selected helical residues of protein G. Here we describe a computationally efficient methodology to include most of the important effects in the calculation of chemical shieldings of backbone ¹⁵N. We analyzed the role of long-range intra-protein electrostatic interactions by comparing models with different complexity in vacuum and in charge field. Our results show that the dipole moment of the α-helix can cause significant deshielding of ¹⁵N; therefore, it needs to be considered when calculating ¹⁵N chemical shielding. We found that it is important to include interactions with the side chains that are close in space when the charged form for ionizable side chains is adopted in the calculation. We also illustrate how the ionization state of these side chains can affect the chemical shielding tensor elements. Chemical shielding calculations using a 8-residue fragment model in vacuum and adopting the charged form of ionizable side chains yield a generally good agreement with experimental data.     

Interatomic potential for Fe–Cr–Ni–N system based on the second nearest-neighbor modified embedded-atom method

The interatomic potential for Fe–Cr–Ni–N system based on the second nearest-neighbour modified embedded-atom method has been developed in this work. The potential is based on those for the corresponding lower order systems. The potential parameters for the binary systems, Cr–N, Ni–N, Ni–Fe and Ni–Cr, were determined by fitting the lattice constants, elastic properties, heat of solution and defect binding energies. The potential parameters for the ternary systems were calculated based on the corresponding binary systems. Then, all of them were applied to the quaternary system Fe–Cr–Ni–N to confirm their validity by a simulation of the lattice constants of AISI 316 austenitic stainless steel with a range of nitrogen content. The results were in good agreement with the previous observations and calculations.     

Switching effect in prey--predator system

Statistical analysis of DNA base sequences generated from nearest neighbor frequencies by a Monte Carlo technique yields distributions of pyrimidine tracts in good agreement with experimental results. Better agreement with experiment is obtained with nearest-neighbor-frequency based calculations than with calculations based on base composition which assume random base arrangements. The nearest-neighbor-frequency method can also be applied to the analysis of high resolution thermal denaturation profiles, the sequence specific interaction of drugs and proteins, and the distribution of photoproducts produced in DNA by ultraviolet radiation.     

Structure,energetics and properties of some molecules with potent anti-HIV activity: a theoretical study

Density functional theory (DFT; B3LYP) and Hartree–Fock (HF; 3-21G, 6-31G(d) and 6-311G(d,p)) calculations with complete geometry optimisations are carried out in the ground state on five 6-aminoquinolone derivatives, which have been proved to be highly effective in inhibiting HIV replication, to study their structures, energetics and HOMO–LUMO correlation with physiological action. The gas-phase calculations and single-point polarisable continuum model water-phase calculations show that the molecules are highly effective in inhibiting HIV replication, which is in excellent agreement with the experiment. Structural features, energies, charge densities and HOMO–LUMO correlation have been found to substantiate the experimental findings. Compound 4 (pyrazine) shows some special features in DFT calculations which are not found in HF calculations. In the present series, HF results are more reliable as expected.     

Mechanism of enzymatic catalysis. Quantum chemistry study of models of serine proteases

The results of molecular orbital calculations for reactions in the active site of serine proteases are outlined. The agreement and disagreement between these results and the theories of enzyme catalysis are discussed.     

Binding free energies for nicotine analogs inhibiting cytochrome P450 2A6 by a combined use of molecular dynamics simulations and QM/MM-PBSA calculations

Molecular dynamics (MD) simulations and hybrid quantum mechanical/molecular mechanical (QM/MM) calculations have been performed to explore the dynamic behaviors of cytochrome P450 2A6 (CYP2A6) binding with nicotine analogs (that are typical inhibitors) and to calculate their binding free energies in combination with Poisson–Boltzmann surface area (PBSA) calculations. The combined MD simulations and QM/MM-PBSA calculations reveal that the most important structural parameters affecting the CYP2A6-inhibitor binding affinity are two crucial internuclear distances, that is, the distance between the heme iron atom of CYP2A6 and the coordinating atom of the inhibitor, and the hydrogen-bonding distance between the N297 side chain of CYP2A6 and the pyridine nitrogen of the inhibitor. The combined MD simulations and QM/MM-PBSA calculations have led to dynamic CYP2A6-inhibitor binding structures that are consistent with the observed dynamic behaviors and structural features of CYP2A6-inhibitor binding, and led to the binding free energies that are in good agreement with the experimentally-derived binding free energies. The agreement between the calculated binding free energies and the experimentally-derived binding free energies suggests that the combined MD and QM/MM-PBSA approach may be used as a valuable tool to accurately predict the CYP2A6-inhibitor binding affinities in future computational design of new, potent and selective CYP2A6 inhibitors.     

A density functional study of (17)O, (14)N and (2)H electric field gradient tensors in the real crystalline structure of alpha-glycine

A density functional theory (DFT) study was carried out to calculate (17)O, (14)N and (2)H electric field gradient (EFG) tensors in accurate neutron diffraction structures of alpha-glycine at 288 and 427 K. B3LYP is the used method and 6-311+G(*) and 6-311++G(**) are the basis sets in the calculations of EFG tensors at the sites of (17)O, (14)N and (2)H nuclei in the monomer and the octameric cluster of alpha-glycine at two temperatures. Quadrupole coupling constants and asymmetry parameters are the converted parameters of calculated EFG tensors to experimentally measurable ones. The calculated results of monomer and the target molecule in octameric cluster reveal that hydrogen-bonding interactions play an important role in the crystalline structure of alpha-glycine where the results of the target molecule in octameric cluster are in good agreement with the experiments.     

Calculation of transmission coefficients for some permeant molecules in human red cell and resting axolemma squid axon membranes

Quantum mechanical calculations of transmission coefficients for some permeant molecules across the human red cell and resting axolemma squid axon membranes are carried out. The calculations depend on (i) the molecular weight of the molecule and (ii) the depth and width of the potential well of the membrane. In most cases good agreement between calculated and experimental values is found.     

Calculation of transmission coefficients for some permeant molecules in human red cell and resting axolemma squid axon membranes

Quantum mechanical calculations of transmission coefficients for some permeant molecules across the human red cell and resting axolemma squid axon membranes are carried out. The calculations depend on (i) the molecular weight of the molecule and (ii) the depth and width of the potential well of the membrane. In most cases good agreement between calculated and experimental values is found.     

The mechanism for isopenicillin N synthase from density-functional modeling highlights the similarities with other enzymes in the 2-His-1-carboxylate family

Isopenicillin N synthase (IPNS) catalyzes a key step in the biosynthesis of the important beta-lactam antibiotics penicillins and cephalosporins. Density-functional calculations with the B3LYP functional are used to propose a detailed mechanism for this reaction. The results support the general scheme outlined from experimental observations, with formation of a four-membered beta-lactam ring followed by formation of a five-membered thiazolidine ring. However, an alternative mechanism for the heterolytic O-O bond cleavage and beta-lactam ring formation steps is proposed. The former part involves protonation of the distal oxygen by an iron-bound water ligand. This mechanism highlights the strong similarities that exist between IPNS and other enzymes of the 2-histidine-1-carboxylate family, especially pterin-dependent amino acid hydroxylases and alpha-keto acid-dependent dioxygenases. Both activation of the cysteine beta-C-H bond by an iron-bound superoxo radical and activation of the valine beta-C-H bond by a ferryl-oxo species show reaction barriers close to the experimentally measured one. These results are in agreement with kinetic isotope experiments that suggest both C-H bond activation steps to be partially rate limiting. The ring formation sequence is determined by the relative strengths of the two C-H bonds. Only the ferryl-oxo intermediate is capable of activating the stronger valine beta-C-H bond.     

Influence of N-H...O and O-H...O hydrogen bonds on the (17)O, (15)N and (13)C chemical shielding tensors in crystalline acetaminophen: a density functional theory study

A computational investigation was carried out to characterize the (17)O, (15)N and (13)C chemical shielding tensors in crystalline acetaminophen. We found that N-H...O and O-H...O hydrogen bonds around the acetaminophen molecule in the crystal lattice have different influences on the calculated (17)O, (15)N and (13)C chemical shielding eigenvalues and their orientations in the molecular frame of axes. The calculations were performed with the B3LYP method and 6-311++G(d, p) and 6-311+G(d) standard basis sets using the Gaussian 98 suite of programs. Calculated chemical shielding tensors were used to evaluate the (17)O, (15)N, and (13)C NMR chemical shift tensors in crystalline acetaminophen, which are in reasonable agreement with available experimental data. The difference between the calculated NMR parameters of the monomer and molecular clusters shows how much hydrogen-bonding interactions affect the chemical shielding tensors of each nucleus. The computed (17)O chemical shielding tensor on O(1), which is involved in two intermolecular hydrogen bonds, shows remarkable sensitivity toward the choice of the cluster model, whereas the (17)O chemical shielding tensor on O(2) involved in one N-H...O hydrogen bond, shows smaller improvement toward the hydrogen-bonding interactions. Also, a reasonably good agreement between the experimentally obtained solid-state (15)N and (13)C NMR chemical shifts and B3LYP/6-311++G(d, p) calculations is achievable only in molecular cluster model where a complete hydrogen-bonding network is considered. Moreover, at the B3LYP/6-311++G(d, p) level of theory, the calculated (17)O, (15)N and (13)C chemical shielding tensor orientations are able to reproduce the experimental values to a reasonably good degree of accuracy.     

Study of the optical properties of a pulse-periodic high-pressure cesium discharge

Results of theoretical and experimental studies of the optical spectrum of a pulse-periodic high-pressure cesium discharge are presented. The results of calculations are in good agreement with experimental data. The possibility of creating an efficient light source based on recombination emission from the discharge plasma is demonstrated. The formation mechanisms of the continuous spectrum of discharge radiation are considered.