Theoretical studies on conformational preferences of model modified nucleic acid base N6-(N-alanylcarbonyl) adenine

Conformational preferences of model modified nucleic acid base N⁶-(N-alanylcarbonyl) adenine, ac⁶Ade, have been investigated using the quantum chemical PCILO (perturbative configuration interaction using localized orbitals) method. The multidimensional conformational space has been searched using selected grid points formed by combining the various torsion angles that take favored values derived from energy variation with respect to each torsion angle individually. The preferred molecular structure is stabilized by an intramolecular hydrogen bond from N(11)H of the amino acid to N(1) of the adenine. The observed crystal structure conformations for the naturally occurring, anticodon adjacent, threonyl analogs, tc⁶Ade, correspond to the predicted most stable conformation for the model modified base ac⁶Ade. Three stable, low energy conformations differing in the orientations of the carboxyl group and the amino acid side chain are predicted within 1 kcal/mol of the most stable structure. The possible bifurcated hydrogen bonding of N(11)H with N(1) and either of the carboxyl oxygens is of minor significance. The indicated orientational flexibility for the carboxyl group and the amino acid side chain may enable convenient probing of the molecular environment, in the vicinity of the anticodon in tRNA, by the amino acid substituent, with only modest changes in energy stabilization.     

Evolutionary Algorithm-Based Crystal Structure Prediction for Copper(I) Fluoride

Despite numerous experimental studies since 1824, the binary copper(I) fluoride remains unknown. A crystal structure prediction has been carried out for CuF using the USPEX evolutionary algorithm and a dispersion-corrected hybrid density functional method. In total about 5000 hypothetical structures were investigated. The energetics of the predicted structures were also counter-checked with local second-order Møller–Plesset perturbation theory. Herein 39 new hypothetical copper(I) fluoride structures are reported that are lower in energy compared to the previously predicted cinnabar-type structure. Cuprophilic Cu−Cu interactions are present in all the low-energy structures, leading to ordered Cu substructures such as helical or zig-zag-type Cu−Cu motifs. The lowest-energy structure adopts a trigonal crystal structure with space group P3₁21. From an electronic point of view, the predicted CuF modification is a semiconductor with an indirect band gap of 2.3 eV.     

Structure and Biosynthesis of Xenoamicins from Entomopathogenic Xenorhabdus

During the search for novel natural products from entomopathogenic Xenorhabdus doucetiae DSM17909 and X. mauleonii DSM17908 novel peptides named xenoamicins were identified in addition to the already known antibiotics xenocoumacin and xenorhabdin. Xenoamicins are acylated tridecadepsipeptides consisting of mainly hydrophobic amino acids. The main derivative xenoamicin A ( 1 ) was isolated from X. mauleonii DSM17908, and its structure elucidated by detailed 1 D and 2 D NMR experiments. Detailed MS experiments, also in combination with labeling experiments, confirmed the determined structure and allowed structure elucidation of additional derivatives. Moreover, the xenoamicin biosynthesis gene cluster was identified and analyzed in X. doucetiae DSM17909, and its participation in xenoamicin biosynthesis was confirmed by mutagenesis. Advanced Marfey’s analysis of 1 showed that the absolute configuration of the amino acids is in agreement with the predicted stereochemistry deduced from the nonribosomal peptide synthetase XabABCD. Biological testing revealed activity of 1 against Plasmodium falciparum and other neglected tropical diseases but no antibacterial activity.     

Glycine Dimers: Structure,Stability, and Medium Effects

We report a study on different ionization states and conformations of the bimolecular (Gly)₂ system by means of quantum mechanical calculations. Optimized geometries for energy minima of the glycine dimer, as well as relative energies and free energies were computed as a function of the medium: gas phase, nonpolar polarizable solvent, and aqueous solution. The polarizable continuum model was employed to account for solvation effects. Energy calculations were done using the MP2/aug‐cc‐pVTZ and B3LYP/6‐311+G(2df,2p) methods on B3LYP/6‐31+G(d,p) optimized structures (some single‐point energy calculations were also done using the B3PW91 and PBE1KCIS methods). Ionized forms of the glycine dimer (either zwitterion–zwitterion or neutral–zwitterion) are predicted to exist in all media, in contrast to amino acid monomers. In aqueous solution, dimerization is an exergonic process (?4 kcal mol^?1). Thus, according to our results, zwitterion–zwitterion Gly dimers might be abundant in supersaturated glycine aqueous solutions, a fact that has been connected with the structure of α‐glycine crystals but that remains controversial in the literature. Another noticeable result is that zwitterion–zwitterion interactions are substantially underestimated when computed using methods based on density functional theory. For comparison, some calculations for the dimer of the simplest chiral amino acid alanine were done as well and differences to the glycine dimer are discussed.     

Theoretical Study of the Structure and the Physico Chemical Properties of 1,2-Benzyne

The structure of 1,2-benzyne (I) has been optimized with respect to its total molecular energy using the MINDO/2 SCF-procedure. The results indicate a bond length of ～1.26 Å for the strained triple bond. The overall geometry suggests that I possesses considerable resonance energy. The calculated heat of formation (ΔHf(I) = 107 kcal/mole) is in good agreement with an estimate from mass spectrometric studies (ΔHf^exp(I) = 118 ± 5 kcal/mole). From model calculations for bent acetylene the strain energy of I is estimated to be about 60 kcl/mole. Some chemical reactions of I are discussed in the light of the results.     

用概率统计法估算天花粉蛋白的二级结构

本文应用Levitt提出的蛋白质中氨基酸对二级结构的特定偏爱的统计方法估算天花粉蛋白的二级结构。计算结果表明,在天花粉蛋白中α-螺旋为32％,β-折叠为28％,反转为20％,其他类型为20％。这一计算结果与X射线衍射研究、圆二色性谱研究的结果相近。     

Dynamical Structure Factor of Fluid Ar36

Abstract

The continued fraction representation of the correlation function and a secant hyperbolic form of the memory function have been used to calculate the dynamical structure factor S(q, ω) of fluid Ar³⁶ for the densities ranging from n? = 0.668 to 0.763 and a temperature to 120 K. The parameters of the memory function have been determined from the fourth and sixth frequency sum rules of S(q, ω). The predicted results for S(q, ω) have been compared with recent neutron scattering data. A good agreement has been achieved. Further, it is also found that the position of first minima of full width at half maxima of S(q, ω) shifts towards smaller wave number side with decrease in density while, the position of first maxima is independent of density.     

Fast and accurate methods for predicting short-range constraints in protein models

Protein modeling tools utilize many kinds of structural information that may be predicted from amino acid sequence of a target protein or obtained from experiments. Such data provide geometrical constraints in a modeling process. The main aim is to generate the best possible consensus structure. The quality of models strictly depends on the imposed conditions. In this work we present an algorithm, which predicts short-range distances between Cα atoms as well as a set of short structural fragments that possibly share structural similarity with a query sequence. The only input of the method is a query sequence profile. The algorithm searches for short protein fragments with high sequence similarity. As a result a statistics of distances observed in the similar fragments is returned. The method can be used also as a scoring function or a short-range knowledge-based potential based on the computed statistics.     

Structure and associated properties of concentrated SiO2 sols in dilute salt solutions

Using the Verwey-Overbeek potential (VO) function the various liquid-state properties of SiO₂ sols in dilute salt solutions have been evaluated under the mean spherical model approximation (MSMA). The structure factors of these SiO₂ sols predicted by this model are compared with results obtained from small-angle neutron scattering experiments by Ramsay et al. Fourier transformation of these structure factors have been performed to obtain the radial distribution functions (RDF), and from these RDF's we computed coordination numbers of the sol particles. The interparticle distanced _c of sol particles has been obtained from the peak position in structure factorS(k) by using the Bragg's equation. The surface potential _s of the oxide sols has been determined from the amplitude (A) of the VO potential. The present calculations clearly indicate some sort of ordering in the sols system. It is gratifying to note that the present theoretical calculations could reproduce the available observed results very satisfactorily with respect to structure factor and other data.     

Structure and morphology of nylon 46 lamellar crystals: Electron microscopy and energy calculations

A detailed electron microscopy study of the structure and morphology of lamellar crystals of nylon 46 obtained by crystallization from solution has been carried out. Electron diffraction of crystals supported by X‐ray diffraction of their sediments revealed that they consist of a twinned crystal lattice made of hydrogen‐bonded sheets separated 0.376 nm and shifted along the a‐axis (H‐bond direction) with a shearing angle of 65°. The interchain distance within the sheets is 0.482 nm. These parameters are similar to those previously described for nylon 46 lamellar crystals grown at lower temperatures. A combined energy calculation and modeling simulation analysis of all possible arrangements for the crystal‐packing of nylon 46 chains, in fully extended conformation, was performed. Molecular mechanics calculations showed very small energy differences between α (alternating intersheet shearing) and β (progressive intersheet shearing) structures with energy minima for successive sheets sheared at approximately 1/6 c and 1/3 c. A mixed lattice composed of a statistical array of α and β structures with such sheet displacements was found to be fully compatible with experimental data and most appropriate to describe nylon 46 lamellar crystals. Annealing of the crystals at temperatures closely below the Brill transition induced enrichment in β structure and increased chain‐folding order. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 41–52, 2000     

A new method for side-chain conformation prediction using a Hopfield network and reproduced rotamers

We present a new side-chain prediction method based on energy minimization using a Hopfield network, focusing on the buried residues of proteins. In this method, the network is composed of automata assigned to each rotamer to restrict side-chain conformational space. We reproduced a rotamer library that enabled us to more widely cover the space for side-chain conformations than those previously produced. The accuracy of the side-chain modeling was estimated by three standards: root mean square deviations (rmsds) between the modeled and the crystal structures, the percentages of correctly predicted side-chain torsion angles, and the percentages of correctly predicted hydrogen bonds. The average rmsd for buried side chains of 21 proteins was 1.10 Å. The value was almost always improved relative to the previous works. The percentage of side-chain X₁ angles for buried residues was 87.3%. By considering the hydrogen bond energy, the average percentage of correctly predicted hydrogen bonds rose from 33% without hydrogen bond energy to 52% with the bond energy. We applied this method to homology modeling, where the protein backbone used to predict side-chain conformations deviates from the correct conformation, and could predict side-chain conformations as correctly as those using the correct backbones. © 1996 by John Wiley & Sons, Inc.     

Identification of thermostabilizing mutations for a membrane protein whose three‐dimensional structure is unknown

We recently developed a physics‐based method for identifying thermostabilizing mutations of a membrane protein. The method uses a free‐energy function F where the importance of translational entropy of hydrocarbon groups within the lipid bilayer is emphasized. All of the possible mutations can rapidly be examined. The method was illustrated for the adenosine A_2a receptor (A_2aR) whose three‐dimensional (3D) structure experimentally determined was utilized as the wild‐type structure. Nine single mutations and a double mutation predicted to be stabilizing or destabilizing were checked by referring to the experimental results: The success rate was remarkably high. In this work, we postulate that the 3D structure of A_2aR is unknown. We construct candidate models for the 3D structure using the homology modeling and select the model giving the lowest value to the change in F on protein folding. The performance achieved is only slightly lower than that in the recent work. © 2016 Wiley Periodicals, Inc.     

Predicted Influence of N-Acetyl Group Content on the Conformational Extension of Chitin and Chitosan Chains

ABSTRACT

Conformational analysis of chitosan molecules has been performed using the MM3(92) force field to investigate the role played by the acetamido groups on the stiffness of these chains. A high dielectric constant value was needed to model an aqueous environment and to reproduce the distribution of the N-acetyl glucosamine group orientation that is observed by NMR. Disaccharidic fragments, differently substituted at C2, were selected as models for chitin and chitosan chains. Their conformational space has been explored by means of adiabatic mapping of the glycosidic Φ,Ψ torsion angles. Although the overall features of all the potential energy surfaces created appear similar, the accessible conformational space of a glycosidic bond is affected by the nature of the substituent at C2 on the non-reducing residue of the disaccharide unit. This is illustrated by the differences in the calculated partition functions together with the predicted average homonuclear and heteronuclear coupling constants. Computed maps were used to predict polymeric unperturbed dimensions, characteristic ratio and persistence length of idealized chitin and chitosan chains, by Monte Carlo methods. Pure chitosan is predicted to be more coiled than pure chitin chains. At low N-acetyl group contents, chain extension appears to be dependent on the degree of substitution. Average chain dimensions increase monotonically for increases in content up to 60% of N-acetyl groups, but show no significant variation at higher contents. For molecules consisting of 50% amino and 50% N-acetylated residues, random, alternate and block patterns of substitution have been investigated. It has also been shown that the spatial extension of the polymer chains is dependent on the primary structure. Comparison with the literature experimental data is difficult because of the extreme diversity of the reported conformationally dependent values. However, such study provides a unique insight into the dependence of these two factors (degree of acetylation and distribution of acetyl groups) on the stiffness and flexibility of different chitin and chitosan chains.     

Aplysiasecosterol A: A 9,11‐Secosteroid with an Unprecedented Tricyclic γ‐Diketone Structure from the Sea Hare Aplysia kurodai

A new 9,11‐secosteroid having an unprecedented tricyclic γ‐diketone structure, aplysiasecosterol A ( 1 ), was isolated from the sea hare Aplysia kurodai. The structure was determined by one‐ and two‐dimensional NMR spectroscopic analysis, molecular modeling studies, a comparison of experimental and calculated ECD spectra, and a modified Mosher′s method. Aplysiasecosterol A ( 1 ) exhibited cytotoxicity against human myelocytic leukemia HL‐60 cells. A biosynthetic pathway for 1 from a known cholesterol was proposed and includes twice α‐ketol rearrangements and an intramolecular acetalization.     

Crystal and Molecular Structure of an Iodo-derivative of the Cyclic Undecapeptide Cyclosporin A

The crystal structure of an iodo-derivative of cyclosporin A has been determined in order to elucidate the constitution of this cyclic undecapeptide. Crystals of iodocyclosporin A are monoclinic, a = 10.475(5), b = 19.60(1), c = 21.04(1) Å, β 99.35(2)°, space group P2₁ (C, No. 4). The structure was solved by the heavy atom method and refined by block-diagonal least-squares analysis to a final R-factor of 0.135 with hydrogen atoms in calculated positions. The cyclic peptide has a conformation which is partly β-pleated sheet and partly open loop. The structure analysis demonstrates for the first time the reality of a new type of dipeptide hydrogen-bonding, predicted by Pullman from MO calculations and leading to a conformation described by him as C.     

Electronic Structure of 3d-Metal Impurities in Silicon Oxynitride

The electronic structure and nature of chemical bonding in orthorhombic Si₂N₂O with substitution impurities (all 3d-atoms) in the cation sublattice have been investigated by the self-consistent ab initio discrete variation method. Consistent changes in the energy structure, interatomic interaction parameters, effective atomic charges, and local moments of substitution 3d-impurities in the series under study are discussed.     

Modeling of density of aqueous solutions of amino acids with the statistical associating fluid theory

The density of aqueous solutions of amino acids has been modeled with the statistical associating fluid theory (SAFT) equation of state. The modeling is accomplished by extending the previously developed new method to determine the SAFT parameters for amino acids. The modeled systems include α-alanine/H₂O, β-alanine/H₂O, proline/H₂O, l-asparagine/H₂O, l-glutamine/H₂O, l-histidine/H₂O, serine/H₂O, glycine/H₂O, alanine/H₂O/sucrose, dl-valine/H₂O/sucrose, arginine/H₂O/sucrose, serine/H₂O/ethylene glycol, and glycine/H₂O/ethylene glycol. The density of binary solutions of amino acids has been correlated or predicted with a high precision. And then the density of multicomponent aqueous solutions of amino acids has been modeled based on the modeling results of binary systems, and a high accuracy of density calculations has been obtained. Finally, the water activities of dl-valine/H₂O, glycine/H₂O, and proline/H₂O have been predicted without using binary interaction parameters, and good results have been obtained.     

Crystal Structure and Quantum Chemical Ab Initio Calculations of Ibotenic Acid,an Excitatory Amino Acid Receptor Agonist

Ibotenic acid, a constituent of Amanita muscaria, is a potent NMDA receptor agonist. The structure of the ibotenic acid zwitterion monohydrate in the crystalline state has been determined by X-ray crystallography. The crystal structure has two ibotenic acid monohydrate formula units in the asymmetric unit and features an extensive hydrogen bond network. The ibotenic acid zwitter-ions in the crystalline state are compared to the in vacuo structure calculated by quantum chemical ab initio calculations at the HF/6-31+G* level and the effects of the hydrogen bond network on the structures in the solid state are discussed. The calculated potential energy curve with respect to side-chain orientation displays a single energy minimum. The conformations corresponding to the solid-state conformations are calculated to be ca. 2 kcal/mol higher in energy than the minimum-energy conformation in vacuo.