Effect of microsolvation on zwitterionic glycine: an ab initio and density functional theory study

The effect of microsolvation on zwitterionic glycine, considering both (-NH3(+)) as proton donor and (-COO(-)) as proton acceptor at correlated ab initio (MP2) level and density functional methods (B3LYP, PW91, MPW1PW91 and PBE) using 6-311++G** basis set has been reported. DFT methods have been employed so as to compare the performance/quality of different gradient-corrected correlation functionals (PW91, PBE), hybrid functionals (B3LYP, MPW1PW91) and to predict the near quantitative structural and vibrational properties, at reduced computational cost. B3LYP method outperforms among the different DFT methods for the computed hydrogen bond distances and found closer to the value obtained by correlated MP2 level, whereas MPW1PW91 and PBE methods shows very similar values but approximately 0.03 A less, compared to B3LYP method. MP2 calculation and single point CCSD(T)//MP2 calculation have been considered to decompose the interaction energy, including corrections for basis set superposition error (BSSE). Moreover, charge distribution analysis has also been carried out to understand the long raised questions, how and why the two body energies have significant contribution to the total binding energy.     

Ab initio conformational analysis of nucleic acid components: intrinsic energetic contributions to nucleic acid structure and dynamics

In recent years, the use of high-level ab initio calculations has allowed for the intrinsic conformational properties of nucleic acid building blocks to be revisited. This has provided new insights into the intrinsic conformational energetics of these compounds and its relationship to nucleic acids structure and dynamics. In this article we review recent developments and present new results. New data include comparison of various levels of theory on conformational properties of nucleic acid building blocks, calculations on the abasic sugar, known to occur in vivo in DNA, on the TA conformation of DNA observed in the complex with the TATA box binding protein, and on inosine. Tests of the Hartree-Fock (HF), second-order M?ller-Plesset (MP2), and Density Functional Theory/Becke3, Lee, Yang and Par (DFT/B3LYP) levels of theory show the overall shape of backbone torsional energy profiles (for gamma, epsilon, and chi) to be similar for the different levels, though some systematic differences are identified between the MP2 and DFT/B3LYP profiles. The east pseudorotation energy barrier in deoxyribonucleosides is also sensitive to the level of theory, with the HF and DFT/B3LYP east barriers being significantly lower (approximately 2.5 kcal/mol) than the MP2 counterpart (approximately 4.0 kcal/mol). Additional calculations at various levels of theory suggest that the east barrier in deoxyribonucleosides is between 3.0 and 4.0 kcal/mol. In the abasic sugar, the west pseudorotation energy barrier is found to be slightly lower than the east barrier and the south pucker is favored more than in standard nucleosides. Results on the TA conformation suggest that, at the nucleoside level, this conformation is significantly destabilized relative to the global energy minimum, or relative to the A- and B-DNA conformations. Deoxyribocytosine would destabilize the TA conformation more than other bases relative to the A-DNA conformation, but not relative to the B-DNA conformation.     

Interactions of hydrated IIa and IIb group metal cations with thioguanine-cytosine DNA base pair: Ab initio and density functional theory investigation of polarization effects, differences among cations, and flexibility of the cation hydration shell.

The structures and energies of the thioguanine-cytosine Watson-Crick (thioGC WC) base pair interacting with hydrated IIa (Mg2+, Ca2+, Ba2+) and IIb group (Zn2+, Cd2+, Hg2+) cations have been studied using ab initio techniques. Furthermore, complexes between guanine and thioguanine with hydrated cations have been characterized assuming various structures of the hydration shells. The complexes of the thioGC WC base pair with hydrated cations have similar properties as the previously studied GC WC base pair. There is substantial polarization stabilization of the base pairing due to cation binding which amounts to 7 - 11 kcal/mol. Soft Cd2+ and Hg2+ cations have a uniquely strong interaction with the thiogroup and induce substantial nonplanarity of the pairing. The thiogroup tends to reduce the number of water molecules in the first hydration shell of the cation. All complexes were optimized within the Hartree-Fock (HF) approximation while their energetics has been evaluated using the second-order Moller-Plesset perturbational method (MP2). All interaction energy evaluations and a substantial portion of the optimizations of the hydrated cation-(thio)guanine complexes have been repeated using Becke-3LYP Density Functional Theory method. All three approximations used (HF, Becke-3LYP, and MP2) give qualitatively the same results for the present cationic complexes. The results demonstrate specific differences among the cations and provide a set of reference structures and energies for verification and/or parametrization of empirical potentials and other theoretical methods.     

Molecular conformational analyses of dehydroalanine analogues

The conformational preferences of dehydroalanine (ΔAla) were examined through ab initio calculations. The geometries of the minimum energy conformations for N-formyldehydro alanilamide and N-acetyl-N′-methylamide of dehydroalanine were determined by gradient optimization at the HF/6-31G* level, and correlation corrections were examined with MP2 single-point energy calculations. Furthermore, HF/3-21G ab initio geometry optimizations were performed on nine conformations of the model tripeptide N-acetyl-N′-methylamide of didehydroalanine. The results indicate that the C₅ is the lowest energy conformation at all levels of theory. However, the relative energy of the helix conformation decreases when the number of ΔAla residues in the peptide chain increases. On the other hand, significant variations of the geometry upon conformational change were observed for the three compounds investigated. These results permit to extract important conformationally dependent geometry trends. The results of this study were compared to x-ray diffraction data on single crystals of dehydroalanine-containing peptides. © 1995 John Wiley & Sons, Inc.     

Concerning the solvent effect in the tautomerism of uracil, 5-fluorouracil, and thymine by density-functional theory and ab initio calculations

The tautomerism of uracil, 5-fluorouracil, and thymine has been investigated in the gas phase and in solution. Electron correlation effects were included in ab initio computations at the MP2 level, and DFT calculations were performed using the B3LYP level. Full geometry optimizations were conducted at the HF/6-31G**, HF/6-31+G**, and B3LYP/6-31+G** levels. Single-point MP2/6-31+G** calculations were performed on the HF/6-31+G** optimized geometries. The influence of the solvent was examined from self-consistent reaction field calculations performed with )=2.21 (1,4-dioxane) and )=78.54 (water). The calculated relative free energies ((G) indicate that substitution of uracil at the position group does not change the relative free energy order of the uracil tautomers in the gas phase and in 1,4-dioxane (except at the MP2 level) whereas this ordering changes in water. Attachment of a fluorine atom changes the relative free energy order of uracil tautomers in the gas phase and in solution.     

Quantum-mechanical computations on the electronic structure of trans-resveratrol and trans-piceatannol: a theoretical study of the stacking interactions in trans-resveratrol dimers

Accurate quantum-chemical calculations based on the second-order M?ller-Plesset perturbation method (MP2) and density functional theory (DFT) were performed for the first time to investigate the electronic structures of trans-resveratrol and trans-piceatannol, as well as to study the stacking interaction between trans-resveratrol molecules. Ab initio MP2 calculations performed with using standard split-valence Pople basis sets led us to conclude that these compounds have structures that deviate strongly from planarity, whereas the DFT computations for the same basis sets revealed that the equilibrium geometries of these bioactive polyphenols are planar. Furthermore, the results obtained at the MP2(full)/aug-cc-pVTZ and B3LYP/aug-cc-pVTZ levels indicated that the geometries of trans-resveratrol and trans-piceatannol are practically planar at their absolute energy minima. The relative energies of the equilibrium geometries of trans-resveratrol on its potential energy surface were computed at the MP2(full)/aug-cc-pVTZ level. According to the results obtained, a T-shaped (edge-to-phase) conformer of trans-resveratrol dimer is the most stable in vacuum. This T-shaped conformer is mainly stabilized by strong hydrogen bonding and weak C-H...π interactions. Stacked structures with parallel-displaced trans-stilbene skeletons were also found to be energetically stable. The vertical separation and twist angle dependencies of the stacking energy were investigated at the MP2(full)/aug-cc-pVTZ, B3LYP/aug-cc-pVTZ, and HF/aug-cc-pVTZ levels. The standard B3LYP functional and the Hartree-Fock method neglect long-range attractive dispersion interactions. The MP2 computations revealed that the London dispersion energy cannot be neglected at long or short distances. The stacked model considered here may be useful for predicting the quantum nature of the interactions in π-stacked systems of other naturally occurring stilbenoids, and can help to enhance our understanding of the antioxidant and anticancer activities of trans-resveratrol.     

Density functional conformational study of 2-O-sulfated 3,6 anhydro-α-D-galactose and of neo-κ- and ι-carrabiose molecules in gas phase and water

We examined the conformational preferences of the 2-O-sulfated-3,6-α-D-anhydrogalactose (compound I) and two 1,3 linked disaccharides constituting-κ or ι-carrageenans using density functional and ab initio methods in gas phase and aqueous solution. Systematic modifications of two torsion angles leading to 324 and 144 starting geometries for the compound I and each disaccharide were used to generate adiabatic maps using B3LYP/6-31G(d). The lower energy conformers were then fully optimized using B3LYP, B3PW91 and MP2 with several basis sets. Overall, we discuss the impact of full relaxation on the energy and structure of the dominant conformations, present the performance comparison with previous molecular mechanics calculations if available, and determine whether our results are impacted, when polarization and diffuse functions are added to the 6-31G(d) basis set, or when the MP2 level of theory is used.     

Conformational stability and normal coordinate analyses for 1-halovinyl azides CH<Subscript>2</Subscript>=CX–NNN (X is F,Cl and Br)

The conformational behavior of 1-halovinyl azides CH2=CX-NNN (X=F, Cl and Br) were investigated by DFT-B3LYP and ab initio MP2 calculations with the 6-311++G** basis set. The molecules were predicted to exist predominantly in the trans (the vinyl CH2=CH- and the azide -NNN groups are trans to each other) conformation. The relative energy between cis and trans were calculated to decrease in order: bromide>chloride>fluoride. Full optimization was performed at the ground and transition states in the molecule at both MP2 and B3LYP levels. The barrier to internal rotation around the C-N single bond in the three molecules was calculated to be about 4-5 kcal mol(-1). The vibrational frequencies were computed at the DFT-B3LYP level and the calculated infrared and Raman spectra of the cis- trans mixture of the three molecules were plotted. Complete vibrational assignments were made on the basis of normal coordinate calculations for both stable conformers of the three molecules.     

The influence of the peptide bond on the conformation of amino acids: a theoretical and FT-IR matrix-isolation study of N-acetylproline

A combined experimental matrix-isolation FT-IR and theoretical study has been performed to investigate the conformational behavior of N-acetylproline. The conformational landscape of N-acetylproline was explored using successively higher computational methods, i.e. HF, DFT(B3LYP) and finally MP2. The exploration resulted in 10 conformations with a relative energy difference smaller than 22 kJ.mol(-1) at the HF/3-21G level of theory. These conformations led to six different conformations after DFT(B3LYP) optimizations. Further optimization at the MP2/6-31++G** level of theory resulted in the same six conformations, all of them with an energy difference smaller than 11.5kJ.mol(-1). One conformation with an intramolecular H-bond was found which was energetically the most favorable conformation. The vibrational and thermodynamical features were calculated using the DFT and MP2 methodologies. In the experimental matrix-isolation FT-IR spectrum, the most stable conformation was dominant and at least two non-H-bonded conformations could be identified. An experimental rotamerization constant between the H-bonded and the other non-H-bonded conformations was estimated and appeared to agree reasonably well with the theoretical MP2 predictions. Some new spectral features of N-acetylproline compared to proline were discovered which might be used to discriminate between the acetylated and non-acetylated form.     

The calculation of structural,elastic and phase stability properties of minerals using first principles techniques: A comparison of HF,DFT and Hybrid functional treatments of exchange and correlation

We benchmark the performance of four treatments of electron exchange and correlation in the prediction of structural and elastic properties of a range of minerals. The treatments used are the Hartree-Fock (HF) theory, the local density approximation (LDA) and the generalised gradient approximation (GGA) to the density functional theory (DFT) and Becke's three parameter hybrid functional (B3LYP). We find that the hybrid functional, B3LYP method yields computed elastic properties in significantly better agreement to experiment than HF or DFT-LDA and performs at least as well, if not better than the most successful DFT-GGA functionals. We suggest that B3LYP is a simple, reliable and computationally efficient tool for the ab initio simulation of mineral systems.     

Low-energy conformers of pamidronate and their intramolecular hydrogen bonds: a DFT and QTAIM study

Extensive DFT and ab initio calculations were performed to characterize the conformational space of pamidronate, a typical pharmaceutical for bone diseases. Mono-, di- and tri-protic states of molecule, relevant for physiological pH range, were investigated for both canonical and zwitterionic tautomers. Semiempirical PM6 method were used for prescreening of the single bond rotamers followed by geometry optimizations at the B3LYP/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels. For numerous identified low energy conformers the final electronic energies were determined at the MP2/6-311++G(2df,2p) level and corrected for thermal effects at B3LYP level. Solvation effects were also considered via the COSMO and C-PCM implicit models. Reasonable agreement was found between bond lengths and angle values in comparison with X-ray crystal structures. Relative equilibrium populations of different conformers were determined from molecular partition functions and the role of electronic, vibrational and rotational degrees of freedom on the stability of conformers were analyzed. For no level of theory is a zwitterionic structure stable in the gas-phase while solvation makes them available depending on the protonation state. Geometrically identified intramolecular hydrogen bonds were analyzed by QTAIM approach. All conformers exhibit strong inter-phosphonate hydrogen bonds and in most of them the alkyl-amine side chain is folded on the P-C-P backbone for further hydrogen bond formation.

Peptide bond distortions from planarity: new insights from quantum mechanical calculations and peptide/protein crystal structures

By combining quantum-mechanical analysis and statistical survey of peptide/protein structure databases we here report a thorough investigation of the conformational dependence of the geometry of peptide bond, the basic element of protein structures. Different peptide model systems have been studied by an integrated quantum mechanical approach, employing DFT, MP2 and CCSD(T) calculations, both in aqueous solution and in the gas phase. Also in absence of inter-residue interactions, small distortions from the planarity are more a rule than an exception, and they are mainly determined by the backbone ψ dihedral angle. These indications are fully corroborated by a statistical survey of accurate protein/peptide structures. Orbital analysis shows that orbital interactions between the σ system of C(α) substituents and the π system of the amide bond are crucial for the modulation of peptide bond distortions. Our study thus indicates that, although long-range inter-molecular interactions can obviously affect the peptide planarity, their influence is statistically averaged. Therefore, the variability of peptide bond geometry in proteins is remarkably reproduced by extremely simplified systems since local factors are the main driving force of these observed trends. The implications of the present findings for protein structure determination, validation and prediction are also discussed.     

Study of the hydrogen bond in different orientations of adenine-thymine base pairs: An <Emphasis Type="Italic">ab initio</Emphasis> study

In order to gain deeper insight into structure, charge distribution, and energies of A-T base pairs, we have performed quantum chemical ab initio and density functional calculations at the HF (Hartree-Fock) and B3LYP levels with 3-21G*, 6-31G*, 6-31G**, and 6-31++G** basis sets. The calculated donor-acceptor atom distances in the Watson-Crick A-T base pair are in good agreement with the experimental mean values obtained from an analysis of 21 high resolution DNA structures. In addition, for further correction of interaction energies between adenine and thymine, the basis set superposition error (BSSE) associated with the hydrogen bond energy has been computed via the counterpoise method using the individual bases as fragments. In the Watson-Crick A-T base pair there is a good agreement between theory and experimental results. The distances for (N2...H23-N19), (N8-H13...O24), and (C1...O18) are 2.84, 2.94, and 3.63 A, respectively, at B3LYP/6-31G** level, which is in good agreement with experimental results (2.82, 2.98, and 3.52 A). Interaction energy of the Watson-Crick A-T base pair is -13.90 and -10.24 kcal/mol at B3LYP/6-31G** and HF/6-31G** levels, respectively. The interaction energy of model (9) A-T base pair is larger than others, -18.28 and -17.26 kcal/mol, and for model (2) is the smallest value, -13.53 and -13.03 kcal/mol, at B3LYP/6-31G** and B3LYP/6-31++G** levels, respectively. The computed B3LYP/6-31G** bond enthalpies for Watson-Crick A-T pairs of -14.4 kcal/mol agree well with the experimental results of -12.1 kcal/mol deviating by as little as -2.3 kcal/mol. The BSSE of some cases is large (9.85 kcal/mol) and some is quite small (0.6 kcal/mol).     

Quantum chemical investigation of intramolecular thione-thiol tautomerism of 1,2,4-triazole-3-thione and its disubstituted derivatives

The one step intramolecular thione-thiol tautomerism of 1,2,4-triazole-3-thione and its disubstituted derivatives has been studied through the use of electronic structure methods. Due to the absence of experimental data for the parent molecule of 1,2,4-triazole-3-thione the structure and energetics of aforementioned tautomers were derived using various basis sets and levels including HF, B3LYP, and MP2 methods. The gas phase results show that in all different levels of theory the most stable tautomer is the thione form. It has also been revealed that B3LYP/6-31G(d,p) level is quite well suited and reliable to investigate these kinds of tautomerism. To account the influence of substituents on the mentioned tautomerization, the tautomerism and conformational properties as well as vibrational analysis of 20 halophenyl and isopyridyl derivatives were investigated using B3LYP/6-31G(d,p) calculations. In all cases the calculations indicate that substituents have no considerable effects on relative stabilities and energy barriers for the thione-thiol proton transfer and the thione forms are the predominant species in the gas phase. In order to figure out the relative stabilities of the species involved in the tautomerism, geometrical and natural bond orbital (NBO) analyses have been employed. It has also been shown that the computed vibrational frequencies of tautomers with different scaling factors could be used to interpret the vibrational frequencies in IR spectrum of similar species.     

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.     

Ab initio quantum mechanical models of peptide helices and their vibrational spectra

Structural parameters for standard peptide helices (alpha, 3(10), 3(1) left-handed) were fully ab initio optimized for Ac-(L-Ala)(9)-NHMe and for Ac-(L-Pro)(9)-NHMe (poly-L-proline-PLP I and PLP II-forms), in order to better understand the relative stability and minimum energy geometries of these conformers and the dependence of the ir absorption and vibrational CD (VCD) spectra on detailed variation in these conformations. Only the 3(10)-helical Ala-based conformation was stable in vacuum for this decaamide structure, but both Pro-based conformers minimized successfully. Inclusion of solvent effects, by use of the conductor-like screening solvent model (COSMO), enabled ab initio optimizations [at the DFT/B3LYP/SV(P) level] without any constraints for the alpha- and 3(10)-helical Ala-based peptides as well as the two Pro-based peptides. The geometries obtained compare well with peptide chain torsion angles and hydrogen-bond distances found for these secondary structure types in x-ray structures of peptides and proteins. For the simulation of VCD spectra, force field and intensity response tensors were obtained ab initio for the complete Ala-based peptides in vacuum, but constrained to the COSMO optimized torsional angles, due to limitations of the solvent model. Resultant spectral patterns reproduce well many aspects of the experimental spectra and capture the differences observed for these various helical types.     

Ab initio study of phenyl benzoate: structure,conformational analysis,dipole moment,IR and Raman vibrational spectra

The molecular structure (bond distances and angles), conformational properties, dipole moment and vibrational spectroscopic data (vibrational frequencies, IR and Raman intensities) of phenyl benzoate were calculated using Hartree–Fock (HF), density functional (DFT), and second order Møller–Plesset perturbation theory (MP2) with basis sets ranging from 6-31G* to 6-311++G**. The theoretical results are discussed mainly in terms of comparisons with available experimental data. For geometric data, good agreement between theory and experiment is obtained for the MP2, B3LYP and B3PW91 levels with basis sets including diffuse functions. The B3LYP/6-31+G* theory level estimates the shape of the experimental functions for phenyl torsion around the Ph–O and Ph–C bonds well, but reproduces the height of the rotational barriers poorly. The B3LYP/6-31+G* harmonic force constants were scaled by applying the scaled quantum mechanical force field (SQM) technique. The calculated vibrational spectra were interpreted and band assignments were reported. They are in excellent agreement with experimental IR and Raman spectra.Figure Calculated and experimental (GED) potential energy functions for torsional motion of phenyl benzoate relative to the minimum value. a The potential function for torsion about the O₃–C₄ bond. b The potential function for torsion about the C₂–C₁₀ bond.     

Multipole electrostatic potential derived atomic charges in NDDO-methods with <Emphasis Type="Italic">spd</Emphasis>-basis sets

The recently introduced multipole approach for computing the molecular electrostatic potential (MEP) within the semiempirical neglect of diatomic differential overlap (NDDO) framework [Horn AHC, Lin Jr-H., Clark T (2005) Theor Chem Acc 114:159–168] has been used to obtain atomic charges of nearly ab initio quality by scaling the semiempirical MEP. The parameterization set comprised a total of 797 compounds and included not only the newly parameterized AM1* elements Al, Si, P, S, Cl, Ti, Zr, and Mo but also the standard AM1 elements H, C, N, O and F. For comparison, the ZDO-approximated MEP was also calculated analytically in the spd-basis. For the AM1*-optimized structures, single-point calculations at the B3LYP, HF and MP2 levels with the 6-31G(d) and LanL2DZP basis sets were performed to obtain the MEP. The regression analysis of all 12 combinations of semiempirical and ab initio MEP data yielded correlation coefficients of at least 0.99 in all cases. Scaling the analytical and multipole-derived semiempirical MEP by the regression coefficients yielded mean unsigned errors below 2.6 and 1.9 kcal mol⁻¹, respectively. Subsequently, for 22 drug molecules from the World Drug Index, atomic charges were computed according to the RESP procedure using XX/6-31G(d) (XX=B3LYP, HF, MP2) and scaled AM1* multipole MEP; the correlation coefficients obtained are 0.83, 0.85 and 0.83, respectively. Figure: Schematic representation of the atomic charge generation: The molecular electrostatic potential (MEP) is calculated using the AM1* Hamiltonian; then the semiempirical MEP is scaled to DFT or ab initio level, and atomic charges are generated subsequently by the restraint electrostatic potential (RESP) fit method. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorized users. Proceedings of “Modeling Interactions in Biomolecules II”, Prague, September 5th–9th, 2005.