Quantum chemical studies on the conformational structure of bacterial peptidoglycan. II. PCILO calculations on the mono-saccharides

Conformational energy calculations were performed on mono-saccharides of the glycan moiety of bacterial peptidoglycan using PCILO semiempirical quantum chemical method to re-examine the preferred conformations of these molecules so far reported in the empirical studies. The PCILO dihedral angles for some side groups are different from those found in MNDO studies. However, in almost every case the PCILO and empirical calculations suggest the same orientations for the different side groups. Moreover, the strengths of the hydrogen bonds between several groups found in the PCILO calculations are more than those of the empirical and MNDO results.     

Modelling of the Sodium Complex of a Calixarene Tetraester in the 1,3-Alternate Conformation

This paper describes the use of molecular mechanics to model the geometry of the sodium complex of a calix[4]arene tetraester, in the 1,3-alternate conformation 1. Partial charges were assigned to the calixarene on the basis of semi-empirical (AM1, PM3, MNDO, INDO, CNDO and ZINDO) calculations and the binding of the sodium ion to the calixarene was modelled using molecular mechanics. Agreement between the optimised and X-ray structures of the complex was very good. The effect of placing the cation in different starting positions on the energy-minimised geometry of the complex is described.     

Quantum chemical studies on the conformational structure of bacterial peptidoglycan. I. MNDO calculations on the glycan moiety

Semi-empirical quantum chemical calculations at MNDO level of approximations have been carried out on the monosaccharide and disaccharide moiety of bacterial peptidoglycan to determine the energetically favoured conformation of their side groups and the relative orientations of sugar rings. The results have been compared with those obtained from empirical energy calculations. The MNDO results have also been discussed with available experimental data and suggest that a chitin-like structure is not favoured for the glycan moiety of peptidoglycan.     

On the performance of semiempirical MO theory for dipole moments of dye molecules

The dipole moments of a set of 71 simple dye molecules calculated at the ab initio, DFT, and semiempirical levels have been compared. The DFT dipole moments are on average 16% larger than those obtained by MP2/6-31G**. AM1 and PM3 modified with an empirical correction procedure yield dipole moments essentially at the same level of accuracy as the results of non-empirical calculations. INDO/S and CNDO/S are considerably less accurate. Among different versions of spectral methods, the CISD scheme gives the best performance.Electronic Supplementary Material available.     

Incorporation of lone pairs into the electrostatic term in the empirical intra- and intermolecular energy calculations

The method hitherto used for estimating the electrostatic term in empirical intramolecular calculations of stable conformations of biologically important molecules and macromolecules and intermolecular calculations of molecular associations or packing energy in molecular crystals had been analyzed. It has been shown that the contribution of atomic hybridization moments is omitted in the calculation of electrostatic interactions from net atomic charges localized on nuclei which have been determined by standard quantum-chemical methods. This contribution plays an important part in determining electrostatic interactions, mainly in molecules containing atoms with lone pairs. Simultaneously, a modified method for calculating the electrostatic term comprising the interaction of the lone pairs, which are represented by atomic hybridization moments, has been proposed. The relationship between the atomic hybridization moment and the bond angle has been expressed for some typical configurations occurring in biologically important molecules. Finally, this new approach is illustrated by results of the conformational analysis of some model compounds for biomolecules and compared with the approach used so far for the estimation of the electrostatic interaction in empirical methods of calculation of the intra- and intermolecular energy.     

The Influence of Charge Calculation on Molecular Dynamics Simulation of Adenine in Water

Abstract

Molecular dynamics simulations of an aqueous solution of adenine have been performed using different methods of charge calculation to evaluate the influence of the values of the atomic charges on the dynamical results and to incorporate new information about the interaction between adenine and water. Four sets of partial charges where computed using ab-initio methods. In all cases the hydration properties of adenine were similar. These results support the view that the simulations by molecular dynamics, at least for the regime of infinite dilution, are not sensitive with respect to the different sets of partial charges used. A net hydrophobic behavior of the adenine molecule, on the water was observed.     

Theoretical investigations on the conformation of 1,5,N(4)-tetramethylcytosine

Theoretical investigations (Perturbative Configuration Interaction over Localized Orbitals (PCILO) and Intermediate Neglect of Differential Overlap (INDO) methods) of the conformation of tetramethylcystosine, an overcrowded molecule with planar struture, have carried out. The Physical features of rotational bending potentials of the dimethylamimo group are discussed. Particulary, the controversial problem concerning the planarity of the molecule is investigated. The obtained results show that the planarity of tetrathylcytosine is an intrinsic property of the molecule. Nevertheless, because of the repulsion between the methyl groups, the planar structure of tetramethylcytosine is slightly destabilized. Further, the functional dependence of the dipole moment of tetramethylcytosine on rotation and bending of the dimethylamino group has been analyzed.     

Theoretical analysis of deoxycytidine-5'-phosphate protonation

The electron density distribution in deoxycytidine-5'-monophosphate (5'-dCMP) molecule and dianion has been studied by the method of CNDO/2. The comparison between the results of calculation for the neutral molecule and the data obtained by Pearlman and Kim shows that there is a linear correlation between the atomic charges calculated using quantum chemistry and those derived from X-ray results. However, partial charges for the deoxyribose fragment are correlated in a nonlinear manner. The influence of the protons added to the cytosine and phosphate residues on the atomic charges and bond orders of deoxy-cytidine-5'-monophosphate has been analyzed here. The conclusion has been drawn that the semiempirical quantum-chemical CNDO/2 technique is applicable to the mononucleotide studies.     

A theoretical study of acriflavin-DNA binding

A theoretical study of binding behaviour of acriflavin, a well-known mutagen, with DNA base pairs such as AT, GC, TA and CG has been performed using CNDO/2 method to compute net atomic charges and dipoles located at various centres in acriflavine as well as base pairs. Acriflavine-DNA base pair interactions have been evaluated using second order perturbation method with multicentered multipole approximation. Only minimum energy configurations have been reported. Results have been discussed with a view to obtain a comparative behaviour of other similar dyes like proflavine and acridine orange.     

Molecular orbital calculations on the conformation of polypeptides and proteins. V. Conformational energy maps and stereochemical rotational states of aliphatic residues

The quantum-mechanical calculations by the PCILO method on the conformation of amino acid residues of proteins have been extended to the valyl, leucyl, and isoleucyl residues. In distinction to the earlier “empirical” computations, the quantum-mechanical results indicate very similar energy contours for the stable conformations of the three residues. Their general outline is also similar to that of the alanyl residue, although reduced by about 25%. Contrary to the “empirical” computations, the present results predict that the region corresponding to the α-helix should be one of great stability for the three residues and in particular for the valyl residue. The quantum-mechanical results are in excellent agreement with the experimental conformations of the aliphatic residues in lysozyme and myoglobin. Their prediction as to the ready availability of the valyl residue in the α-helical conformation agrees moreover with Ptitsyn's statistical evaluation of the participation of this residue in the inner turns of the helical regions in six globular proteins. The maximum conformational space allowed for the aliphatic residues is somewhat smaller than that allowed for the aromatic ones, while the minimum conformational space (region of stability common to all the residues) is similar in both groups.     

The nonplanar peptide unit. III. Quantum chemical calculations for related compounds and experimental X-ray diffraction data.

The possible nonplanar distortions of the amide group in formamide, acetamide, N-methylacetamide, and N-ethylacetamide have been examined using CNDO/2 and INDO methods. The predictions from these methods are compared with the results obtained from X-ray and neutron diffraction studies on crystals of small open peptides, cyclic peptides, and amides. It is shown that the INDO results are in good agreement with observations, and that the dihedral angles θ_N and Δω defining the nonplanarity of the amide unit are correlated approximately by the relation θ_N = ?2Δω, while θ_C is small and uncorrelated with Δω. The present study indicates that the nonplanar distortions at the nitrogen atom of the peptide unit may have to be taken into consideration, in addition to the variation in the dihedral angles (?,ψ), in working out polypeptide and protein structures.     

Barrier to rotation and conformation of the NB2 group in cytosine and its derivatives. Part I. Theoretical study of cytosine.

A theoretical investigation of the conformation of the amino group in cytosine has been performed by the CNDO/2 and INDO methods. The results suggest that from the energetical point of view the conformation of the amino group is not stable in the course of rotation. It changes its hybridization from sp2-like in the planar case to sp3-like in the transition state. The physical basis of the barrier to rotation of this group around the C4-N7 bond are discussed. Some comments on the solvent dependence of the electronic absorption spectra of cytosine are presented.     

Spatial configuration of single-stranded polynucleotides. Calculations of average dimensions and Nmr coupling constants

The probability distributions of the torsional angles (Φ′, ω′, ω, Φ, and ψ), which fix the structure of nucleotide backbone, have been calculated using the results of energy calculations based on extended Huckel theory (EHT), complete neglect of differential overlap (CNDO), perturbative configuration interaction using localized orbitals (PCILO), and classical potential functions (CPF) methods. Statistical average values of the vicinal ¹H? ¹H, ¹H? ³¹P, and ¹³C? ³¹P nmr coupling constants 〈J〉 have been calculated from the generalized Karplus relations using the probability distribution in the Φ′, Φ, and ψ space. Experimental 〈J〉 values for polyribouridylic acid (polyU) support the theoretical predictions for these torsional angles. Using Monte Carlo technique, random coils of single-stranded polynucleotides have been simulated and the mean-square end-to-end distance 〈r²〉 has been calculated. Molecular orbital methods (EHT, CNDO, and PCILO) suggest considerable flexibility around O? P bonds, leading to fairly small values for the characteristic ratio (C_∞ ～ 4). Observed values of the unperturbed characteristic ratio for polynucleotides are quite large (C_∞ ～ 18) suggesting a relatively rigid nucleotide backbone. The results based on molecular orbital calculations can be reconciled with the experimental values by introducing an additional stabilization of ～2 kcal mol^?1 for the predicted minimum energy ragion (Φ′ ～ 240°, ω′ ～ 290°, ω 290°, Φ 180°, and ψ 60°). Such a stabilization may arise from the association of water molecules and metal ions with the phosphate group and (or) Coulomb interaction between neighboring phosphate groups. The calculations provide a semiquantitative estimate of torsional rigidity in the nucleotide backbone.     

An optimized potential function for the calculation of nucleic acid interaction energies I. Base stacking

An optimized potential function for base-stacking interaction is constructed. Stacking energies between the complementary pairs of a dimer are calculated as a function of the rotational angle and separation distance. Using several different sets of atomic charges, the electrostatic component in the monopole-monopole approximation (MMA) is compared to the more refined segmented multipole–multipole representation (SMMA); the general features of the stacking minima are found to be correctly reproduced with IEHT or CNDO atomic charges. The electrostatic component is observed to control the location of stacking minima. The MMA, in general, is not a reliable approximation of the SMMA in regions away from minima; however, the MMA is reliable in predicting the location and nature of stacking minima. The attractive part of the Lennard-Jones 6–12 potential is compared to and parameterized against the expression for the second-order interaction terms composed of multipole-bond polarizability for the polarization energy and transition-dipole bond polarizabilities for approximation of the dispersion energy. The repulsive part of the Lennard-Jones potential is compared to a Kitaygorodski-type repulsive function; changing the exponent from its usual value of 12 to 11.7 gives significantly better agreement with the more refined repulsive function. Stacking minima calculated with the optimized potential method are compared with various perturbation-type treatments. The optimized potential method yields results that compare as well with melting data as do any of the more recent and expensive perturbation methods.     

PM3 and AM1 Study on β-N-acetyl-muramic Acid and 3 Murein Related Derivatives

The energetically favoured conformations of -N-acetyl-Muramic acid, its C6-O-acetylated form, the methylamide and the methyl-glycoside have been investigated using the semiempirical PM3 and AM1 methods. All these compounds are either components or fragmentary structures of the murein network. The atomic coordinates of the starting set of the -N-acetyl-Muramic acid molecule have been obtained by a PM3 minimization of one saccharide molecule cut out from the murein single strand model proposed by Barnickel at al. [1]. The sidegroups of the derivatives have been introduced by a molecular editor. These conformations served as starting points in conformational space for a grid search by scanning all sidechain torsional angles for non-hydrogen atoms with exception of the N-acetyl group which was held in cisoid position (i.e. N2-H bond is parallel to C1-H and C3-H bond) and only minimized. The PM3 method with an additional amide correction potential and the AM1 method were used. The torsional angle distributions of the lactyl sidechain (free acid and methylamide), the C6-O-acetylated sidechain and the C1-methoxy sidechain have been investigated, showing distinct energetically favoured torsional angle regions. The results are compared to earlier studies on -N-acetyl-Muramic acid by J.S. Yadav et al. [2,3] who were using the MNDO and PCILO methods and by P.N.S. Yadav et al. [4] who were using the empirical MM2 force-field.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1007/s0089460020190     

Theoretical study of the distal-side steric and electrostatic effects on the vibrational characteristics of the FeCO unit of the carbonylheme proteins and their models.

The vibronic theory of activation and quantum chemical intermediate neglect of differential overlap (INDO) calculations are used to study the activation of carbon monoxide (change of the C-O bond index and force field constant) by the imidazole complex with heme in dependence on the distortion of the porphyrin ring, geometry of the CO coordination, iron-carbon and iron-imidazole distances, iron displacement out of the porphyrin plane, and presence of the charged groups in the heme environment. It is shown that the main contribution to the CO activation stems from the change in the sigma donation from the 5 sigma CO orbital to iron, and back-bonding from the iron to the 2 pi orbital of CO. It follows from the results that none of the studied distortions can explain, by itself, the wide variation of the C-O vibrational frequency in the experimentally studied model compounds and heme proteins. To study the dependence of the properties of the FeCO unit on the presence of charged groups in the heme environment, the latter are simulated by the homogeneous electric field and point charges of different magnitude and location. The results show that charged groups can strongly affect the strength of the C-O bond and its vibrational frequency. It is found that the charges located on the distal side of the heme plane can affect the Fe-C and C-O bond indexes (and, consequently, the Fe-C and C-O vibrational frequencies), both in the same and in opposite directions, depending on their position. The theoretical results allow us to understand the peculiarities of the effect of charged groups on the properties of the FeCO unit both in heme proteins and in their model compounds.     

Quantum chemical study of relative reactivities of a series of amines and nitriles: Relevance to prebiotic chemistry

Using the Iterative Extended Hucken Theory (IEHT) calculations of the elctron distribution and orbital energies of a series of thirteen amines, nitriles and amino-nitriles relevant to prebiotic and cosmo-chemistry have been carried out. Ground state properties such as the energy and nature of the highest occupied (HOMO) and lowest empty (LEMO) molecular orbitals, net atomic charges and number of non-bonding electrons have been identified as criteria for correlating the relative nucleophilicity of amine and nitrile nitrogens and the electrophilicity of nitrile and other unsaturated carbon atoms. The results of such correlations can be partially verified by known chemical behavior of these compounds and are used to predict and understand their role in prebiotic organic synthesis.     

Barrier to rotation and conformation of the -NR2 group in cytosine and its derivatives. Part II. Experimental and theoretical dipole moments of methylated cytosines.

The dipole moments of several cytosine, methylaminocytosine and dime-thylaminocytosine derivatives with and without an ortho methyl group were determined experimentally in dioxane and benzene. Calculations of total energies and dipole moments were performed by the CNDO/2 and INDO methods for sp2 and sp3 hybridization of exocyclic nitrogen for different values of rotational angle phiC-N. Comparison of the experimental dipole moments with those calculated for the energy minima suggests that the conformation of the dimethylamino group is not planar and differs from that found in cytosine. 1,5,7-Trimethylcytosine, with the dipole moment of 7 Deby units, was considered to be the model compound which closely reproduces the dipole moment of cytosine.     

The preparation of fully N-epsilon-acetimidylated cytochrome c.

We have re-examined the acetimidylation and subsequent deprotection of cytochrome c by published methods in the light of recent findings on the tendency of protein acetimidylation reactions to yield side products of differing net charges. We find that the protection methods do indeed yield a mixture of products, some of which have considerably diminished biological activity. Our observations support a postulated mechanism for the generation of side products, and we have been able to identify the major factor responsible for their formation by published methods. The deprotection method appears to be free of side reactions. We describe a new procedure for acetimidylation that will produce fully N-epsilon-acetimidylated cytochrome c. This derivative, lacking detectable side products and having good biological activity, is useful for structure-function studies and as an intermediate in the semisynthesis of cytochrome c analogues.     

On contribution of known atomic partial charges of protein backbone in electrostatic potential density maps

Partial charges of atoms in a molecule and electrostatic potential (ESP) density for that molecule are known to bear a strong correlation. In order to generate a set of point‐field force field parameters for molecular dynamics, Kollman and coworkers have extracted atomic partial charges for each of all 20 amino acids using restrained partial charge‐fitting procedures from theoretical ESP density obtained from condensed‐state quantum mechanics. The magnitude of atomic partial charges for neutral peptide backbone they have obtained is similar to that of partial atomic charges for ionized carboxylate side chain atoms. In this study, the effect of these known atomic partial charges on ESP is examined using computer simulations and compared with the experimental ESP density recently obtained for proteins using electron microscopy. It is found that the observed ESP density maps are most consistent with the simulations that include atomic partial charges of protein backbone. Therefore, atomic partial charges are integral part of atomic properties in protein molecules and should be included in model refinement.