Values Of Dihedral Angles Research Articles

H2O2–Ng dynamics predictions using an accurate potential energy surface

ABSTRACTBased on ab initio calculations, our research group has built an analytical ground-state potential energy surface (PES) for hydrogen peroxide– noble gas (Ng) interactions, such as H2O2–He, H2O2–Ne, H2O2–Ar, H2O2–Kr, and H2O2–Xe complexes. From this PES, it was verified that the Ng presence does not affect the equilibrium values of the H2O2 dihedral angles. This happens because the H2O2 intramolecular barriers have much higher energies than the atom–bond interaction within these complexes. From this point of view, it is indeed reasonable to consider the H2O2 system as a rigid rotor, frozen at its equilibrium configuration. We present in this work the torsional motion for the H2O2 isolated system, the vibration–rotation energy levels and spectroscopic constants for hydrogen peroxide–noble gas by using the aforementioned PES. The predicted H2O2 torsional motions are in good agreement with both theoretical and experimental results available in the literature. Regarding H2O2–Ng ro-vibrational energies and spectroscopic constants, it is the first time that these calculations are presented in the literature. The current theoretical predictions are expected to be useful in the future experimental investigations.

γ-Turn Mimicry with Benzodiazepinones and Pyrrolobenzodiazepinones Synthesized from a Common Amino Ketone Intermediate.

To investigate diazepinone analogues as γ-turn mimics, seven 1,4-benzodiazepin-2-ones 6 and fourteen pyrrolo[1,2-d][1,4]benzodiazepin-6-ones 4 and 5 were synthesized from 1-(2-aminophenyl)pent-4-en-1-one (7). Acylation of aniline 7 with N-Boc-amino acids, olefin oxidation, Boc removal, and intramolecular Paal-Knorr condensation gave 4 and 5. Alternatively, Boc removal prior to oxidation gave benzodiazepinones 6, which were converted to 4 by ozonolysis and cyclization. Comparison of dihedral angle values for the amino acid component from X-ray analyses of 4g, 5f, and 6f and related diazepinones has catalogued the manner by which ring substituents affect the component's ability to mimic the central residues of γ-turns.

Characterization and comparison of perezone with some analogues. Experimental and theoretical study

Perezone had been used for centuries in the traditional Mexican medicine, it is useful and a handful of illness. Perezone and other derivatives also present activity against certain lines of cancer, such as the myeloblastoid leukemia cell line K-562 and carcinoma cell lines (PC-3 and SKLU-1) with IC50 <10μM. Perezone and isoperezone have shown the major cytotoxic potency. Characterization of perezone was carried out by UV–Visible, IR, DSC, TGA and powder X-ray diffraction, as well as docking studies using caspase-3 structures as receptors. Theoretical studies for optimizing the geometry of perezone were carried out and the results compared with values of single crystal X-ray diffraction. The experimental values of atomic distances, angles and dihedral angles are in good agreement with the theoretical values. Interaction of perezone with the cysteine catalytic site with the caspase-3 was found in the docking studies. A docking study of perezone, with horminone, thymoquinone and isoperezone as ligands and the protein apoptein, caspase-3 as receptor, was carried to demonstrate that the hindrance steric factor, chemical structure and the functional groups are important in the biological activity of these natural products. The docking score energetic values are in good agreement with the experimental cytotoxic results obtained from the experiments when perezone and analogues were studied in different types of cancer.

From the sequence to the conformation of the unabridged transmembrane domains TM1 and TM2 of the cASIC1a ion channel - a parallel tempering approach.

This work was devised to unravel, along replica-exchange molecular-dynamics (REMD) simulations, the conformation in solution of the TM1 and TM2 transmembrane domains of the homotrimeric cASIC1a ion channel. This includes the head of TM1 and tail of TM2 that had previously defied X-ray diffraction analysis in the crystal. The structure of the open-channel complex of cASIC1a with psalmotoxin 1 (PcTx1) was chosen here as a basis, although, to make the simulations affordable, the procedure was limited to the missing portions, including a few adjacent α-helical turns. The latter were held fixed during the simulations. Reassembling the whole subunit, by superimposition of the fixed portions, resulted in diving of both TM1 and TM2 as continuous α-helices into the cytoplasm. At completion of this work, it appeared, from similar X-ray diffraction studies, that TM2 for both the complex of cASIC1a with the coral snake MitTx toxin, and the isolated desensitized ion channel, is discontinuous, with the triad G443-A444-S445 taking an extended, belt-like conformation. In this way, a filter ring against hydrated ions is formed by G443 in the trimer. Our REMD examination of this complex revealed a strong resistance by G443, and only that residue, to take dihedral-angle values compatible with an α-helical conformation. This suggests that the flexibility of glycine alone does not explain formation of the extended, belt-like conformation of the triad G443-A444-S445. This also requires cooperation in the trimer.

Amino Acids in Nine Ligand-Prefer Ramachandran Regions.

Several secondary structures, such as π-helix and left-handed helix, have been frequently identified at protein ligand-binding sites. A secondary structure is considered to be constrained to a specific region of dihedral angles. However, a comprehensive analysis of the correlation between main chain dihedral angles and ligand-binding sites has not been performed. We undertook an extensive analysis of the relationship between dihedral angles in proteins and their distance to ligand-binding sites, frequency of occurrence, molecular potential energy, amino acid composition, van der Waals contacts, and hydrogen bonds with ligands. The results showed that the values of dihedral angles have a strong preference for ligand-binding sites at certain regions in the Ramachandran plot. We discovered that amino acids preceding the ligand-prefer ϕ/ψ box residues are exposed more to solvents, whereas amino acids following ligand-prefer ϕ/ψ box residues form more hydrogen bonds and van der Waals contacts with ligands. Our method exhibited a similar performance compared with the program Ligsite-csc for both ligand-bound structures and ligand-free structures when just one ligand-binding site was predicted. These results should be useful for the prediction of protein ligand-binding sites and for analysing the relationship between structure and function.

Tri-peptide reference structures for the calculation of relative solvent accessible surface area in protein amino acid residues

Relative amino acid residue solvent accessibility values allow the quantitative comparison of atomic solvent-accessible surface areas in different residue types and physical environments in proteins and in protein structural alignments. Geometry-optimised tri-peptide structures in extended solvent-exposed reference conformations have been obtained for 43 amino acid residue types at a high level of quantum chemical theory. Significant increases in side-chain solvent accessibility, offset by reductions in main-chain atom solvent exposure, were observed for standard residue types in partially geometry-optimised structures when compared to non-minimised models built from identical sets of proper dihedral angles abstracted from the literature. Optimisation of proper dihedral angles led most notably to marked increases of up to 54% in proline main-chain atom solvent accessibility compared to literature values. Similar effects were observed for fully-optimised tri-peptides in implicit solvent. The relief of internal strain energy was associated with systematic variation in N, Cα and Cβ atom solvent accessibility across all standard residue types. The results underline the importance of optimisation of ‘hard’ degrees of freedom (bond lengths and valence bond angles) and improper dihedral angle values from force field or other context-independent reference values, and impact on the use of standardised fixed internal co-ordinate geometry in sampling approaches to the determination of absolute values of protein amino acid residue solvent accessibility. Quantum chemical methods provide a useful and accurate alternative to molecular mechanics methods to perform energy minimisation of peptides containing non-standard (chemically modified) amino acid residues frequently present in experimental protein structure data sets, for which force field parameters may not be available. Reference tri-peptide atomic co-ordinate sets including hydrogen atoms are made freely available.

Crystal structure of 1-[(2S*,4R*)-6-fluoro-2-methyl-1,2,3,4-tetra-hydro-quinolin-4-yl]pyrrolidin-2-one.

In the title compound, C14H17FN2O, the 1,2,3,4-tetra-hydro-pyridine ring of the quinoline moiety adopts a half-chair conformation, while the pyrrolidine ring has an envelope conformation with the central methyl-ene C atom as the flap. The pyrrolidine ring lies in the equatorial plane and its mean plane is normal to the mean plane of the quinoline ring system, with a dihedral angle value of 88.37 (9)°. The bridging N-C bond distance [1.349 (3) Å] is substanti-ally shorter than the sum of the covalent radii (d cov: C-N = 1.47 Å and C=N = 1.27 Å), which indicates partial double-bond character for this bond, resulting in a certain degree of charge delocalization. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds, forming sheets lying parallel to (10-1). These two-dimensional networks are linked via C-H⋯F hydrogen bonds and C-H⋯π inter-actions, forming a three-dimensional structure.

(E)-1-([1,1'-Biphen-yl]-4-yl)-3-(2-methyl-phen-yl)prop-2-en-1-one.

In the title mol­ecule, C22H18O, the o-tolyl ring is connected through a conjugated double bond. The mol­ecule adopts an E conformation and the C—C=C—C torsion angle is 178.77 (13)°. The overall conformation may be described by the values of dihedral angles between the different planes. The terminal rings are twisted by an angle of 54.75 (8)°, while the biphenyl part is not planar, the dihedral angle between the planes of the rings being 40.65 (8)°. The dihedral angle between the benzene rings is 14.10 (7)°. There are three weak C—H⋯π inter­actions found in the crystal structure. No classic hydrogen bonds are observed.

Molecular structure of bis(dipyrrolylmethanates) of d-metals according to the quantum chemical calculations by the PM6 method

Quantum chemical calculations of the molecular structure of bis(dipyrrolylmethanates) of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), and mercury(II) of the composition [M2L2] are performed using the PM6 method within the Gaussian 09W program package. The lengths of M-N coordination bonds, the values of dihedral angles formed by N-M-N bonds, the distances lM⋯M between the M⋯M atoms are optimized. It is noted that the regularities obtained from the analysis of the results of quantum chemical calculations of the molecular structure of [M2L2] helicates reliably reflect the main trends of changes in their physicochemical properties depending on the nature of a complexing agent and the features of the ligand structure.

Analysis ofN-amino-imidazolin-2-one peptide turn mimic 4-position substituent effects on conformation by X-ray crystallography

N-Amino-imidazolin-2-ones, a new class of turn mimics onto which side chains of different amino acids may be added conveniently, have been analyzed by X-ray crystallography. 4-Methyl and 4-benzyl N-amino-imidazolin-2-one tetrapeptide models 2 and 3 were examined to study the influence of the 4-position substituent on turn conformation and the chi dihedral angle of the neighbouring C-terminal residue side-chain. The nature of the 4-position substituent caused substantial effects on the ψ(i + 2) main chain and C-terminal Phe χ(1) side-chain dihedral angle values, giving a preference for β- and γ-turn conformers for the methyl- and benzyl-substituted imidazolin-2-ones, respectively. Conformational analysis in the solid state has provided insight to guide application of N-amino-imidazolin-2-ones in peptide mimicry.

Hydrogen-bonded complexes of serotonin with methanol and ethanol: a DFT study

Density functional theoretical studies on hydrogen-bonded complexes of serotonin with methanol/ethanol have been carried out in a systematic way. The conformational analysis led to ten stable conformers that can be either gauche or anti depending on the dihedral angle values taken by ethylamine side chain and the 5-hydroxyl group. Serotonin-molecules strongly bind with ethanol than methanol. Ethylamine side chain is the most reactive site in both methanol/ethanol complexes and it is responsible for the stability order. The topological parameters, electron density, and Laplacian of electron density show excellent correlation with the hydrogen bond length. Natural bond orbital analysis confirms C–H···O hydrogen bond formed between the serotonin–alcohol complexes to be red shift in nature except for Gph(out)anti complex both with methanol and ethanol to be blue shifted. The energy decomposition analysis reveals that strong interactions between serotonin and ethanol/methanol are due to the attractive contributions from the electrostatic component.

On the formation of a refractory skeleton in composite materials. A review

Papers on theoretical and experimental investigations into the formation of a refractory skeleton in composite materials have been analyzed. It has been shown that the critical parameters that describe the refractory skeleton are the contiguity of particles and dihedral angle. In the theory of the formation of a refractory skeleton certain results have been achieved in the establishing of interrelationship between the values of dihedral angle, contiguity, concentration of phases, and the conditions for the skeleton formation. The composition and structure of interphase boundaries of the refractory skeleton have been described and the thickness of the particles contact zone has been substantiated. Various technologies that allow one to actively influence the formation of the refractory skeleton have been considered and ways of the further investigations in the field have been suggested.

Grain growth inhibition in thin nanocrystalline Au films by grain boundary diffusion and oxidation of Ti

We studied grain growth in thin nanocrystalline Au films deposited on a sapphire substrate with and without an ultrathin Ti underlayer (adhesion promoter). The samples were annealed at 200°C for 2h in air. The reference thin Au film without a Ti underlayer exhibited significant grain growth during annealing, whereas no changes in microstructure of the Au layer were observed in the Au/Ti bilayers. This stabilization of the microstructure of the Au layer was attributed to thermal grain boundary grooves on the Au surface filled with Ti oxide. The grooves exhibited an elongated morphology characterized by a low apparent dihedral angle value, atypical for thermal grain boundary grooves in pure metals. We demonstrated that grooves with this morphology are very efficient in pinning grain boundary motion. We also developed a quantitative model of grain boundary grooving coupled with grain boundary interdiffusion in thin bilayer films. The model predicted the formation of long, narrow grooves at the grain boundaries, which are very efficient in suppressing grain growth in nanocrystalline thin films.

Design of Cyclic Peptides Featuring Proline Predominantly in the cis Conformation under Physiological Conditions

Turns are secondary-structure elements that are omnipresent in natively folded polypeptide chains. A large variety of four-residue β-turns exist, which differ mainly in the backbone dihedral angle values of the two central residues i+1 and i+2. The βVI-type turns are of particular biological interest because the i+2 residue is always a proline in the cis conformation and might thus serve as target of peptidyl prolyl cis/trans isomerases (PPIases). We have designed cyclic hexapeptides containing two proline residues that predominantly adopt the cis conformation in aqueous solution. NMR data and MD calculations indicated that the cyclic peptide sequences c-(-DXaa-Ser-Pro-DXaa-Lys-Pro-) result in highly symmetric backbone structures when both prolines are in the cis conformation and the D-amino acids are either alanine or phenylalanine residues. Replacement of the serine residue either by phosphoserine or by tyrosine compromises this symmetry, but further increases the cis conformation content of both prolines. As a result, we obtained a cyclic hexapeptide that exists almost exclusively as the cis-Pro/cis-Pro conformer but shows no cis/trans interconversion even in the presence of the PPIase Pin1, apparently due to an energetically quite favorable but highly restricted conformational space.

Comparative study of spectroscopic properties of the low-lying electronic states of 2,4-pentadien-1-iminium cation and its N-substituted analogues

Semiempirical and ab initio-based CI methods have been employed to study the low-lying electronic states of 2,4-pentadien-1-iminium cation and its N-substituted analogues with electron-donating (methyl, isopropyl) and electron-withdrawing (fluoromethyl) groups on nitrogen. Variations of the dihedral angles (Γ3, Γ4) of the ground state have given the global minima and global maxima at (180°, 180°) and (90°, 0°) conformations, respectively, with some exceptions in the case of fluoromethyl compound. Increase in the +I effect on nitrogen shifts the TICT conical intersection point away from the 90° (Γ3 dihedral angle) value, when the Γ4 value is kept fixed at 180°. Transition moment values of the allowed S0(1Ag –like) →S1 (2Bu–like) transitions are expectedly higher than the forbidden S0(1Ag –like) →S2(2Ag –like) transitions by almost 5.6 D. Radiative lifetime values of the first excited states are calculated to be around 215 ps for all the four compounds. At (180°, 180°) conformation the vertical excitation energy (VEE) between the S0 and S1 states of the 2,4-pentadieniminium cation is found to be 3.3 eV, which corresponds to the absorption wavelength value of roughly 375 nm. The VEE value increases with substituents having +I effect on nitrogen, while for the fluoromethyl compound it is calculated to be around 2.85 eV. The energy gap between the first two excited singlet states is found to have the least value in the isopropyl-substituted compound, where the S2 state contains a huge contribution from the HOMO2→LUMO2 configuration. Substitution of electron-donating groups (methyl, isopropyl) on the nitrogen of 2,4-pentadien-1-iminium cation shifts the TICT conical intersection position (with respect to the Γ3 dihedral angle) away from the 90° value, when Γ4 is kept fixed at 180°. This is due to the stabilization of the covalent-ground state (S0) and destabilization of the first excited singlet state (S1).

Probing the Structure and Dynamics of Proteins by Combining Molecular Dynamics Simulations and Experimental NMR Data.

NMR experiments provide detailed structural information about biological macromolecules in solution. However, the amount of information obtained is usually much less than the number of degrees of freedom of the macromolecule. Moreover, the relationships between experimental observables and structural information, such as interatomic distances or dihedral angle values, may be multiple-valued and may rely on empirical parameters and approximations. The extraction of structural information from experimental data is further complicated by the time- and ensemble-averaged nature of NMR observables. Combining NMR data with molecular dynamics simulations can elucidate and alleviate some of these problems, as well as allow inconsistencies in the NMR data to be identified. Here, we use a number of examples from our work to highlight the power of molecular dynamics simulations in providing a structural interpretation of solution NMR data.

Conformational properties of acidic oligo- and disaccharides and their ability to bind calcium: a molecular modeling study

The conformational analysis of disaccharides composed of two constituents of alginic acid (β-d-mannuronic and α-l-guluronic acids) was performed. Several additional aspects, such as pH and the type of ionic environment were taken into account. The calculations were performed on the two levels of theory: semi-empirical (PM3) conformational search in vacuo and molecular dynamics with explicit solvent based on the biomolecular (GROMOS) force field. The results indicate that the values of glycosidic dihedral angles can vary in a very similar range, independently of the disaccharide composition. The presence of interresidual hydrogen bonds involving carboxyl groups reduces the ability for calcium ion binding. The type and the concentration of cations in the solution do not practically affect the conformation of disaccharides. Both disaccharides and the oligosaccharides composed of corresponding units exhibit a similar degree of conformational flexibility; only in the case of oligosaccharides containing the α-l-guluronate units, the glycosidic bonds are much more rigid when compared to those of disaccharides.

Interactions between CD44 protein and hyaluronan: insights from the computational study

CD44 is a protein, being a major cell surface receptor for hyaluronan (HA). Molecular modeling investigation was carried out on the murine CD44 in complex with a HA heptasaccharide in order to: (i) elucidate the nature and dynamics of interactions between the HA chain and CD44; (ii) find out if the existence of two conformational forms of CD44 discovered in the XRD (X-Ray Diffraction) study can be responsible for its switching between low and high affinity for HA. The results indicate that the contact of CD44 with HA is dominated by hydrogen bonding with small contribution of hydrophobic interactions and salt bridges. In addition, the two ('A' and 'B') conformational forms of the HA-CD44 complex reported experimentally by Banerji et al. cannot be observed during simulations when considering the distance between HA and the sidechain of the R45 residue. There exists, however, a free energy barrier associated with the change of the φ dihedral angle value at Y46. Additionally, some thermodynamic parameters (e.g. the Gibbs free energy change) accompanying the HA binding by CD44 were estimated.

Structural cooperativity in histone H3 tail modifications

Post-translational modifications of histone H3 tails have crucial roles in regulation of cellular processes. There is cross-regulation between the modifications of K4, K9, and K14 residues. The modifications on these residues drastically promote or inhibit each other. In this work, we studied the structural changes of the histone H3 tail originating from the three most important modifications; tri-methylation of K4 and K9, and acetylation of K14. We performed extensive molecular dynamics simulations of four types of H3 tails: (i) the unmodified H3 tail having no chemical modification on the residues, (ii) the tri-methylated lysine 4 and lysine 9 H3 tail (K4me3K9me3), (iii) the tri-methylated lysine 4 and acetylated lysine 14 H3 tail (K4me3K14ace), and (iv) tri-methylated lysine 9 and acetylated lysine 14 H3 tail (K9me3K14ace). Here, we report the effects of K4, K9, and K14 modifications on the backbone torsion angles and relate these changes to the recognition and binding of histone modifying enzymes. According to the Ramachandran plot analysis; (i) the dihedral angles of K4 residue are significantly affected by the addition of three methyl groups on this residue regardless of the second modification, (ii) the dihedral angle values of K9 residue are similarly altered majorly by the tri-methylation of K4 residue, (iii) different combinations of modifications (tri-methylation of K4 and K9, and acetylation of K14) have different influences on phi and psi values of K14 residue. Finally, we discuss the consequences of these results on the binding modes and specificity of the histone modifying enzymes such as DIM-5, GCN5, and JMJD2A.

Statistical analysis of protein molecules

AbstractIn this paper, entropy and auto-correlation values of main chain dihedral angles of 22,356 protein molecules are calculated and found to lie within a well-specified range for most proteins. Also, the entropy values obey a Gaussian distribution, which indicates that entropy plays a crucial role in evolution and conservation of protein tertiary structures. A comparison of the auto-correlation values of the dihedral angles of the entire protein molecule with those of the alpha helices and beta sheets indicates that random coils play an important role in determining the tertiary structure of protein molecules.