Investigations of dipeptide structures containing pyrrolysine as N-terminal residues: a DFT study in gas and aqueous phase

A set of six dipeptides containing pyrrolysine invariably at their N-terminal positions is studied in gas and aqueous phase using a polarizable continuum model (PCM). The molecular geometries of the dipeptides are fully optimized at B3LYP/6-31++G(d,p) level of theory and a second derivative (frequency) analysis confirms that all the optimized geometries are true minima. The effects of solvation and identity of the varying C-terminal residue on the energetics, structural features of the peptide planes, values of the ψ and ? dihedrals, geometry around the α-carbon atoms and theoretically predicted vibrational spectra of the dipeptides are thoroughly analyzed. Solvation effects are found to modify the gas phase conformation of the dipeptides around ψ dihedrals while the identity of the varying C-terminal residue affect the values of ?, planarity of the peptide planes and geometry around the α-carbon atoms. The presence or absence of three types of intramolecular H-bonds, namely O…H–N, N…H–N and O…H–C that leave noticeable signatures in the IR spectra, play crucial roles in influencing the geometry of the peptide planes and in determining the energetics of the dipeptides.     

DFT studies on the structural and vibrational properties of polyenes

Detailed density functional theory (DFT) calculations on the structure and harmonic frequencies of model all-trans and all-cis polyenes were undertaken. For the first time, we report on the convergence of selected B3LYP/6-311++G** and BLYP/6-311++G** calculated structural parameters resulting from a systematic increase in polyene size (chains containing 2 to 14 C?=?C units). The limiting values of the structural parameters for very long chains were estimated using simple three-parameter empirical formulae. BLYP/6-311++G** calculated ν(C?=?C) and ν(C–C) frequencies for all-trans and all-cis polyenes containing up to 14 carbon–carbon double bonds were used to estimate these values for very long chains. Correction of raw, unscaled vibrational data was performed by comparing theoretical and experimental wavenumbers for polyenes chains containing 3 to 12 conjugated C?=?C units with both ends substituted by tert-butyl groups. The corrected ν(C?=?C) and ν(C–C) wavenumbers for all-trans molecules were used to estimate the presence of 9 – 12 C?=?C units in all-trans polyene pigment in red coral.

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Graphical abstract Detailed density functional theory (DFT) calculations on the structure and harmonic frequencies of model all-trans and all-cis polyenes were undertaken. For the first time, we report on the convergence of selected B3LYP/6-311++G** and BLYP/6-311++G** calculated structural parameters resulting from a systematic increase in polyene size (chains containing 2 to 14 C=C units). The limiting values of the structural parameters for very long chains were estimated using simple three-parameter empirical formulae.

     

The effect of intrinsic curvature on conformational properties of circular DNA.

Both thermal fluctuations and the intrinsic curvature of DNA contribute to conformations of the DNA axis. We looked for a way to estimate the relative contributions of these two components of the double-helix curvature for DNA with a typical sequence. We developed a model and Monte Carlo procedure to simulate the Boltzmann distribution of DNA conformations with a specific intrinsic curvature. Two steps were used to construct the equilibrium conformation of the model chain. We first specified the equilibrium DNA conformation at the base pair level of resolution, using a set of the equilibrium dinucleotide angles and DNA sequence. This conformation was then approximated by the conformation of the model chain consisting of a reduced number of longer, straight cylindrical segments. Each segment of the chain corresponded to a certain number of DNA base pairs. We simulated conformational properties of nicked circular DNA for different sets of equilibrium dinucleotide angles, different random DNA sequences, and lengths. Only random sequences of DNA generated with equal probability of appearance for all types of bases at any site of the sequence were used. The results showed that for a broad range of intrinsic curvature parameters, the radius of gyration of DNA circles should be nearly independent of DNA sequence for all DNA lengths studied. We found, however, a DNA properly that should strongly depend on DNA sequence if the double helix has essential intrinsic curvature. This property is the equilibrium distribution of the linking number for DNA circles that are 300-1000 bp in length. We found that a large fraction of the distributions corresponding to random DNA sequences should have two separate maxima. The physical nature of this unexpected effect is discussed. This finding opens new opportunities for joined experimental and theoretical studies of DNA intrinsic curvature.     

Unfolding and conformational studies on bovine adrenodoxin probed by engineered intrinsic tryptophan fluorescence

An intrinsic steady-state fluorescent system for bovine adrenodoxin has been developed to study the protein structure in solution and the processes involved in protein unfolding. Since mature Adx contains no natural Trp residue as internal probe, all of the aromatic amino acids, tyrosine at position 82 and four phenylalanines at positions 11, 43, 59 and 64, were at each case replaced by tryptophan. The resulting single tryptophan containing mutants kept their biological function compared with the wild type. Molecular modeling studies verify thermal unfolding experiments which point to a dramatically reduced stability caused by steric hindrance only for mutant F59W. Fluorescence spectra, Stern-Volmer quenching constants, and fluorescence energy transfer calculations indicated the analyzed positions to be situated in solution in the same immediate environment as in the crystal structure. Unfolding experiments with Gdn-HCl and time-resolved stopped-flow measurements provide evidence for differential stability and a chronologically ordered unfolding mechanism of the different fluorescence probe positions in the protein.     

7,5'-O-dibenzylinosines: synthesis and studies on their conformational properties

Reaction of 2',3'-O-isopropylidene inosine with benzyl bromide (1 h, rt) led to the 1,5'-O-dibenzylderivative 4, but by increasing the reaction time or the temperature, compound 4 is further transformed into the 1,7,5'-O-tribenzylinosine derivative 5. Similarly, the 7-methyl-1,5'-O-dibenzylderivative 6 has been synthesized from 4. The 1H-NMR spectra of 5 and 6 showed peculiar chemical shifts for geminal protons (H5' and H5' of the ribose, and the CH2 of the benzyl groups). Preliminary NMR studies have been performed, including NOESY experiments that point toward the predominant existence of conformers that are stabilized by an electrostatic interaction between the positively charged imidazole of the base moiety and the high electron density of the 5'-benzyl substituent.     

Ab initio conformational maps for disaccharides in gas phase and aqueous solution

Ab initio conformational maps for beta-lactose in both the gas phase and in aqueous solution have been constructed at the HF/6-31G(d,p) level of calculation. The results of the gas-phase ab initio calculations allow us to conclude that a rigid conformational map is able to predict the regions of the minima in the potential energy surface of beta-lactose, in full agreement with those found in the relaxed conformational map. The solvation effects do not give rise to any new local minimum in the potential energy surface of beta-lactose, but just change the relative Boltzmann populations of the conformers found in the gas-phase calculations. The values obtained for heteronuclear spin coupling constant (3J(H,C)), using the seven most stable conformers in solution are in good agreement with the available experimental values. This is a good indication that ab initio rigid conformational maps can be reliably used to sort the most stable conformers of beta-lactose.     

Solid phase synthesis and NMR conformational studies on cyclic decapeptide template molecule

Selectively addressable topological templates represent a key feature in the de novo design of proteins using the TASP concept (Template Assembled Synthetic Proteins). The regioselectively addressable (orthogonally protected) lysine-containing cyclic templates are especially interesting for combinatorial chemistry. We report the synthesis and structural analysis of a series of cyclic and bicyclic decapeptide templates (model of TASP molecules). The peptides were synthesized via solid phase synthesis and followed by solution cyclization. The conformation of the peptides was studied by proton nmr spectroscopy in dimethylsulfoxide and in trifluoroethanol/water. The structure of the peptide template was calculated with the program DIANA and followed by simulated annealing from the nmr experimental constraints. The peptides adopts a fold comprising two beta-strands and two type II beta-turns predicted for conformationally well-defined templates. The design of such a restained cyclic decapeptide template will be discussed along with Regioselectively Addressable Functionalized Template (RAFT) molecular recognition and template for combinatorial synthesis.     

Solid state NMR studies on the structural and conformational properties of natural maize starches

Natural maize starches having a range of amylose contents have been characterised by CP/MAS NMR spectroscopy. Chemical shifts, relative resonance intensities, line-widths and spectral shapes were compared at different moisture contents. At 10% moisture content, these parameters showed few significant differences across a range of apparent amylose levels from 0 to 84%. After hydration of the granules to ≈30% moisture, it was found that the amylose content significantly affected the relative signal intensities and line-widths especially of C-1 and C-4 resonances. Narrower line-widths after hydration were attributed to (i) an increased degree of crystallinity, and (ii) disappearance of the signals of amorphous material which, on becoming more mobile, became invisible to the CP/MAS experiment. The enhanced resolution at higher moisture levels revealed signals which were assigned to the amylose–lipid complex, i.e. V-type amylose. The amount of V-amylose detected by NMR increased with both amylose content and lipid content of the granule. Prolonged treatment of the granules with iodine vapour significantly increased the amount of V-type amylose in the high amylose samples, but caused a decrease in their degree of crystallinity. Waxy-maize starch was barely affected by iodination. The results provide evidence that amylose tends to disrupt the structural order within amylopectin crystallities. This effect is enhanced by the formation of the amylose–iodine complex, indicating that V-amylose could be a major crystallite-disrupting agent in native starch granules.     

The conformational properties of dehydrobutyrine and dehydrovaline: theoretical and solid‐state conformational studies

Dehydrobutyrine is the most naturally occurring dehydroamino acid. It is also the simplest dehydroamino acid having the geometrical isomers E/Z. To investigate its conformational properties, a theoretical analysis was performed on N‐acetyl‐α,β‐dehydrobutyrine N′‐methylamides, Ac‐(E)‐ΔAbu‐NHMe and Ac‐(Z)‐ΔAbu‐NHMe, as well as the dehydrovaline derivative Ac‐ΔVal‐NHMe. The ?, ψ potential energy surfaces and the localised conformers were calculated at the B3LYP/6‐311 + + G(d,p) level of theory both in vacuo and with inclusion of the solvent (chloroform, water) effect (SCRF method). The X‐ray crystal structures of Ac‐(Z)‐ΔAbu‐NHMe and Ac‐ΔVal‐NHMe were determined at 85 and 100 K, respectively. The solid‐state conformational preferences for the studied residues have been analysed and compared with the other related structures. Despite the limitations imposed by the C^α = C^β double bond on the topography of the side chains, the main chains of the studied dehydroamino acids are more flexible than in standard alanine. The studied dehydroamino acids differ in their conformational preferences, which depend on the polarity of the environment. This might be a reason why the nature quite precisely differentiates between ΔVal and each of the ΔAbu isomers, and why, particularly so with the latter, they are used as a conformational tool to influence the biological action of usually small, cyclic dehydropeptides. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Theoretical studies on the tautomerism and intramolecular hydrogen shifts of 5-Amino-tetrazole in the gas phase

The tautomerism and intramolecular hydrogen shifts of 5-amino-tetrazole in the gas phase were studied in the present work. The minimum energy path (MEP) information of 5-amino-tetrazole was obtained at the CCSD(T)/6–311G**//MP2/6–311G** level of theory. The six possible tautomers of 1H, 4H-5-imino-tetrazole (a), 1H-5-amino-tetrazole (b), 2H-5-amino-tetrazole (c), 1H, 2H-5-imino-tetrazole (d), the mesoionic form (e) and 2H, 4H-5-imino-tetrazole (f) were investigated. Among these tautomers, there are 2 amino- forms, 3 imino- forms, and 1 mesoionic structure form. In all the tautomers, 2-H form (c) is the energetically preferred one in the gas phase. In the imino- tautomers, the energy value of the compound d is similar as that of the compound f but it is higher than the energy value of the compound a. The potential energetic surface (PES) and kinetics for five reactions have been investigated. Reaction 2 (b→c) was hydrogen shifts only in which the 1-H and 2-H rearrangement. This means that the reaction 2 (b→c) is energetically favorable having an activation barrier of 45.66 kcal·mol⁻¹ and the reaction energies (ΔE) is only 2.67 kcal·mol⁻¹. However, the reaction energy barrier for tautomerism of reaction 1 (b→e) is 54.90 kcal·mol⁻¹. Reaction 1 (b→a), reaction 3 (c→d), and reaction 5 (c→f) were amino- →imino- tautomerism reactions. The energy barriers of amino- →imino- tautomerism reactions required are 59.39, 65.57, 73.61 kcal·mol⁻¹ respectively in the gas phase. The calculated values of rate constants using TST, TST/Eckart, CVT, CVT/SCT and CVT/ZCT methods using the optimized geometries obtained at the MP2/6–311G** level of theory show the variational effects are small over the whole temperature range, while tunneling effects are big in the lower temperature range for all tautomerism reactions. Graphical Abstract Figure (DOC 45.0 KB)     

Theoretical studies on the conformation of saccharides. XIV. Structure and conformational properties of the glycosylamines

The 2-methylaminotetrahydropyran was used as a model to study conformational properties of the N-glycosidic linkage in glycosylamines. Relaxed two-dimensional conformational (phi, psi) maps in 20 solvents were calculated by a method in which the total energy is divided into the energy of the isolated molecule and the solvation energy. Molecular geometry optimization has been carried out for each conformer using the quantum chemical method PCILO. The calculated variations of the geometry are consistent with the results obtained by the statistical analysis of available experimental data retrieved from the Cambridge Structural Database. The calculated abundances of conformers show that the polarity of the solvent has little effect on the anomeric ratio, and the form having the methylamino group equatorial is favored in all considered solvents.     

Monitoring protein conformational changes by quenching of intrinsic fluorescence

The quenching of intrinsic fluorescence of human serum albumin and pigeon liver malic enzyme by acrylamide was studied after the proteins were denatured to different stages. The progress of protein denaturation induced by guanidine hydrochloride was accompanied by increasing of effective dynamic quenching constant which provides a convenient parameter for monitoring protein conformational change.     

DFT study of the gas phase proton transfer in guanine assisted by water, methanol, and hydrogen peroxide

A computational study of hydrogen-bonded complexes between the oxo-/hydroxo-amino N7/9H tautomers of guanine and water, methanol, and hydrogen peroxide has been performed at the B3LYP/6-31+G(d) level of theory. The mechanisms of the water-, methanol-, and hydrogen peroxide-assisted proton transfers in guanine were studied and compared with the intramolecular proton transfer in guanine in the gas phase. It was found that the assisted proton transfers pass through about three times lower energy barriers than those found for isolated guanine tautomers. Figure DFT study of the gas phase proton transfer in guanine assisted by water, methanol and hydrogen peroxide     

DFT studies of the phenol adsorption on boron nitride sheets

We perform first principles total energy calculations to investigate the atomic structures of the adsorption of phenol (C₆H₅OH) on hexagonal boron nitride (BN) sheets. Calculations are done within the density functional theory as implemented in the DMOL code. Electron-ion interactions are modeled according to the local-spin-density-approximation (LSDA) method with the Perdew-Wang parametrization. Our studies take into account the hexagonal h-BN sheets and the modified by defects d-BN sheets. The d-BN sheets are composed of one hexagon, three pentagons and three heptagons. Five different atomic structures are investigated: parallel to the sheet, perpendicular to the sheet at the B site, perpendicular to the sheet at the N site, perpendicular to the central hexagon and perpendicular to the B-N bond (bridge site). To determine the structural stability we apply the criteria of minimum energy and vibration frequency. After the structural relaxation phenol molecules adsorb on both h-BN and d-BN sheets. Results of the binding energies indicate that phenol is chemisorbed. The polarity of the system increases as a consequence of the defects presence which induces transformation from an ionic to covalent bonding. The elastic properties on the BN structure present similar behavior to those reported in the literature for graphene.     

DFT studies of hydrocarbon combustion on metal surfaces

Catalytic combustion of hydrocarbons is an important technology to produce energy. Compared to conventional flame combustion, the catalyst enables this process to operate at lower temperatures; hence, reducing the energy required for efficient combustion. The reaction and activation energies of direct combustion of hydrocarbons (CH?→?C?+?H) on a series of metal surfaces were investigated using density functional theory (DFT). The data obtained for the Ag, Au, Al, Cu, Rh, Pt, and Pd surfaces were used to investigate the validity of the Brønsted-Evans-Polanyi (BEP) and transition state scaling (TSS) relations for this reaction on these surfaces. These relations were found to be valid (R²?=?0.94 for the BEP correlation and R²?=?1.0 for the TSS correlation) and were therefore used to estimate the energetics of the combustion reaction on Ni, Co, and Fe surfaces. It was found that the estimated transition state and activation energies (E_TS?=??69.70 eV and E_a?=?1.20 eV for Ni, E_TS?=??87.93 eV and E_a?=?1.08 eV for Co and E_TS?=??92.45 eV and E_a?=?0.83 eV for Fe) are in agreement with those obtained by DFT calculations (E_TS?=??69.98 eV and E_a?=?1.23 eV for Ni, E_TS?=??87.88 eV and E_a?=?1.08 eV for Co and E_TS?=??92.57 eV and E_a?=?0.79 eV for Fe). Therefore, these relations can be used to predict energetics of this reaction on these surfaces without doing the time consuming transition state calculations. Also, the calculations show that the activation barrier for CH dissociation decreases in the order Ag ? Au ? Al ? Cu ? Pt ? Pd ? Ni?>?Co?>?Rh?>?Fe.     

Benchmarking the DFT methodology for assessing antioxidant-related properties: quercetin and edaravone as case studies

The overall objective was to identify an accurate computational electronic method to virtually screen phenolic compounds through their antioxidant and free-radical scavenging activity. The impact of a key parameter of the density functional theory (DFT) approach was studied. Performances of the 21 most commonly used exchange-correlation functionals are thus detailed in the evaluation of the main energetic parameters related to the activities of two prototype antioxidants, namely quercetin and edaravone, is reported. These functionals have been chosen among those belonging to three different families of hybrid functionals, namely global, range separated, and double hybrids. Other computational parameters have also been considered, such as basis set and solvent effects. The selected parameters, namely bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) allow a mechanistic evaluation of the antioxidant activities of free radical scavengers. Our results show that all the selected functionals provide a coherent picture of these properties, predicting the same order of BDEs and PDEs. However, with respect to the reference values, the errors found at CBS-Q3 level significantly vary with the functional. Although it is difficult to evidence a global trend from the reported data, it clearly appears that LC-ωPBE, M05-2X, and M06-2X are the most suitable approaches for the considered properties, giving the lowest cumulative mean absolute errors. These methods are therefore suggested for an accurate and fast evaluation of energetic parameters related to an antioxidant activity via free radical scavenging.