The molecular structure of a curl-shaped retinal isomer

Computational studies of retinal protonated Schiff base (PSB) isomers show that a twisted curl-shaped conformation of the retinyl chain is a new low-lying minimum on the ground-state potential energy surface. The curl-shaped isomer has a twisted structure in the vicinity of the C₁₁=C₁₂ double bond where the 11-cis retinal PSB isomerizes in the rhodopsin photoreaction. The twisted configuration is a trapped structure between the 11-cis and all-trans isomers. Rotation around the C₁₀–C₁₁ single bond towards the 11-cis structure is prevented by steric interactions of the two methyl groups on the retinyl chain and by the torsion barrier of the C₁₀–C₁₁ bond in the other direction. Calculations of spectroscopic properties of the 11-cis, all-trans, and curl-shaped isomers provide useful data for future identification of the new retinal PSB isomer. Circular dichroism (CD) spectroscopy might be used to distinguish between the retinal PSB isomers. The potential energy surface for the orientation of the β-ionone ring of the 11-cis retinal PSB reveals three minima depending on the torsion angle of the β-ionone ring. Two of the minima correspond to 6-s-cis configurations and one has the β-ionone ring in 6-s-trans position. The calculated CD spectra for the two 6-s-cis configurations differ significantly indicating that the sign of the β-ionone ring torsion angle could be determined using CD spectroscopy. Calculations of the CD spectra suggest that a flip of the β-ionone ring might occur during the first 1 ps of the photoreaction. Rhodopsin has a negative torsion angle for the β-ionone ring, whereas the change in the sign of the first peak in the experimental CD spectrum for bathorhodopsin could suggest that it has a positive torsion angle for the β-ionone ring. Calculated nuclear magnetic resonance (NMR) shielding constants and infrared (IR) spectra are also reported for the retinal PSB isomers. Figure The figure shows the optimized molecular structure of the curl-shaped retinal isomer. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Study of the Formation and Solution Properties of Worm-Like Micelles Formed Using Both N-Hexadecyl-N-Methylpiperidinium Bromide-Based Cationic Surfactant and Anionic Surfactant

The viscoelastic properties of worm-like micelles formed by mixing the cationic surfactant N-hexadecyl-N-methylpiperidinium bromide (C₁₆MDB) with the anionic surfactant sodium laurate (SL) in aqueous solutions were investigated using rheological measurements. The effects of sodium laurate and temperature on the worm-like micelles and the mechanism of the observed shear thinning phenomenon and pseudoplastic behavior were systematically investigated. Additionally, cryogenic transmission electron microscopy images further ascertained existence of entangled worm-like micelles.     

Geometry of the five-membered ring mathematical demonstration of the pseudorotation formulae

The geometrical relations between the 15 typical parameters (bond lengths and angles, torsion angles) of a five-membered ring are derived for any ring then for a regular one. It is demonstrated that for the case of the 20 symmetrical C ₂ and C _sconformations, only geometrical considerations are needed to obtain the pseudorotation formulae for the torsion angles. However, the puckering intensity as well as the bond angle values cannot be expressed from geometrical constraints alone but would require energetical considerations.     

Conformational analysis of muscimol, a GABA agonist

The potential energy barriers for rotation around the C₅C₆ bond in muscimol and two related isoxazoles have been calculated using the MINDO/3 molecular orbital method. The preferred conformations have N₇C₆C₅C₄ torsion angles near ± 100 °, in agreement with crystallographic data. The activities of muscimol and related isoxazoles as bicuculline-sensitive inhibitors of neuronal firing, however, are best accounted for in terms of “active conformations” with N₇C₆C₅C₄ torsion angles in the range +(32–46) °. These findings predict a limited range of possible “active conformations” for the flexible neurotransmitter GABA at postsynaptic receptors common to GABA, (+)-bicuculline salts and muscimol.     

Molecular Mechanics Studies of Molybdenum Disulphide Catalysts Parameterisation of Molybdenum and Sulphur

Abstract

A method for the parameterisation of molybdenum disulphide is presented which reproduces the crystal structure accurately. The method involves calculating parameters such that there is no net force contribution from any individual term of the potential on any atom. Ideal bond lengths and bond angles are taken from the X-ray crystal structure; stretching and bending force constants are calculated from a combination of spectroscopic data and quantum mechanics calculations, whereby the energy function with bond length or bond angle is calculated and fitted with an harmonic potential. For the non-bonded Lennard-Jones parameters, the dispersion coefficient C was calculated by an interpolation of existing published parameters using a multiple regression and then the crystal energy was minimised with respect to the van der Waals radius r₀ using a fixed crystal fragment.

These parameters were tested for various models of the hexagonal and rhombohedral forms of MoS₂. RMS fits between structures minimised with molecular mechanics and experimental models ranged from 0.006 Å to 0.012 Å.     

Shear rate dependence of free energy barrier height for phenyl ring rotations in polystyrene based on non-equilibrium molecular dynamics simulations

Polystyrene properties are influenced by ring motions in side groups. The main chain conformation and interaction with the surroundings dominate the ring rotations. It is known that shear flow affects linear chain conformation and molecular distribution. However, shear-induced variations in the ring rotations have yet to be studied. This study presents a shear flow system of polystyrene via non-equilibrium molecular dynamics simulations. The free energy barrier of the phenyl ring rotations was obtained from the distribution of angle χ between the ring and main chain based on the Boltzmann distribution law. The results showed that the barrier height approaches a constant value at a shear rate less than 10¹⁰ s^? 1, but decreases with an increase in shear rate higher than 10^10.5 s^? 1. Furthermore, the radial distribution function and potential energies were compared. Remarkably, the shear flow reduced the bond vibrations of the phenyl rings, but increased the separation between intermolecular particles. Hence, a smaller cavity is necessary for the rings to rotate once but more volume is occupied by the rings. The smaller volume obtained via main chain motions needed to construct the cavity lowers the energy barrier height at shear rate higher than 10^10.5 s^? 1.     

Oxidative Inhibition of Protein Phosphatase 2A Activity: Role of Catalytic Subunit Disulfides

A molecular basis for the inhibition of brain protein phosphatase 2A (PP2A) activity by oxidative stress was examined in a high-speed supernatant (HSS) fraction from rat cerebral cortex. PP2A activity was subject to substantial disulfide reducing agent-reversible inhibition in the HSS fraction. Results of gel electrophoresis support the conclusions that inhibition of PP2A activity was associated with the both the disulfide cross-linking of the catalytic subunit (PP2A_C) of the enzyme to other brain proteins and with the formation of an apparent novel intramolecular disulfide bond in PP2A_C. Additional findings that the vicinal dithiol cross-linking reagent phenylarsine oxide (PAO) produced a potent dithiothreitol-reversible inhibition of PP2A activity suggest that the cross-linking of PP2A_C vicinal thiols to form an intramolecular disulfide bond may be sufficient to inhibit PP2A activity under oxidative stress. We propose that the dithiol–disulfide equilibrium of a vicinal thiol pair of PP2A_C may confer redox sensitivity on cellular PP2A.     

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.     

Strong effect of the interaction potential cut-off on the crystallinity of films grown by simulations

The paper deals with the methodology of film growth simulations using classical molecular dynamics and an empirical interaction potential. We focus on the effect of the cut-off distance (r_C) of the short-range part of the potential. On the one hand, we find that r_C does not affect the qualitative conclusions of the simulations and that its quantitative effect is in the logical direction (better crystallinity at higher r_C). On the other hand, we show that the aforementioned quantitative effect is very strong, and clearly underestimated in the literature. The film crystallinity is affected by (non-)neglecting of as seemingly low energies as several meV per bond. The results are important for the design of growth simulations of crystalline films and for the correct interpretation of their results.     

On the conformational dependence of the proton chemical shifts in nucleosides and nucleotides. I. Proton shifts in the ribose ring of pyrimidine nucleosides as a function of the torsion angle about the glycosyl bond

Molecular orbital computations are performed on the different contributions to the variation of the chemical shifts of the non-exchangeable protons of the ribose ring in pyrimidine nucleosides as a function of the torsion angle X_CN about the glycosyl bond. They show that the ring current effects are negligible, that the contribution of the atomic diamagnetic anisotropy is important for protons which come at very short distances to the anisotropic group (C₂ = 0₂) and that the polarization effect may have a determining influence on the sign of the variation of the chemical shift. The theoretical results are discussed in relation to the experimental findings on the differences between the chemical shifts of the ribose protons of pyrimidine nucleosides methylated at C₅ and C₆.     

The J-coupling Restrained Molecular Mechanics (JrMM) Protocol - An Efficient Alternative for Deriving DNA Endocyclic Torsion Angle Constraints Part II: Experimental Application of the JrMM Protocol

Abstract

The J-coupling restrained molecular mechanics (JrMM) protocol, which correlates deoxyribose endocyclic torsion angles and vicinal proton-proton torsion angle φ_{1′ 2′} in Part I of this study, is demonstrated to be a viable alternative to efficiently derive the endocyclic torsion angle constraints for the determination of the solution structures of DNA molecules. Extensive testing demonstrating the validity of the JrMM-derived torsion angle constraints in the restrained molecular dynamics and energy minimization structural refinement processes is performed theoretically using an energy-minimized B-DNA model and experimentally using a DNA hexamer d(CGTACG)₂. The results show that only a 0.2 Å difference exists between the RMSD values of the refined structures using the ideal and the JrMM-derived endocyclic torsion angle constraints. The JrMM-derived torsion angles are also determined to be in good agreement with the torsion angles derived through the use of the vicinal J-derived torsion angles. These results show that through the use of reliably measured J_{1′ 2′} values and computer simulation method, the endocyclic torsion angle constraints can be derived reliably and efficiently. Thus the JrMM method serves as an alternative strategy to generate endocyclic torsion angle constraints for the determination of the solution structures of DNA molecules.     

Proton transfer dynamics in the propionic acid dimer from path integral molecular dynamics calculations

The double proton transfer process in the cyclic dimer of propionic acid in the gas phase was studied using a path integral molecular dynamics method. Structures, energies and proton trajectories were determined. Very large amplitude motions of the skeleton of a propionic acid molecule were observed during the simulations, and almost free rotation of the C₂H₅ group around the C_α-C bond. A double-well symmetric potential with a very small energy barrier was determined from the free energy profile for the proton motions. Infrared spectra for different isotopomers were calculated, and comparative vibrational analysis was performed. The vibrational results from CPMD appear to be in qualitative agreement with the experimental ones.     

Association of Brain Protein Phosphatase 1 with Cytoskeletal Targeting/Regulatory Subunits

Abstract: Protein phosphatase 1 catalytic subunit (PP1_C) is highly enriched in isolated rat postsynaptic densities. Gel overlay analyses using digoxigenin (DIG)-labeled PP1_C revealed four major rat brain PP1_C-binding proteins (PP1bps) with molecular masses of ≈216, 175, 134, and 75 kDa, which were (1) more abundant in brain than other rat tissues; (2) differentially expressed in microdissected brain regions; and (3) enriched in isolated cortex postsynaptic densities. PP1bp175, PP1bp134, PP1bp75, and PP1_C were partially released from forebrain particulate extracts by incubation at low ionic strength, which destabilizes the actin cytoskeleton. Size-exclusion chromatography of solubilized extracts separated two main PP1 activities (≈600 and ≈100 kDa). PP1bps and PP1_Cγ₁ were enriched in the ≈600-kDa peak, but PP1_Cβ was enriched in the ≈100-kDa peak. Furthermore, PP1bp175 and PP1bp134 exhibited lower binding of recombinant DIG-PP1_Cβ than recombinant DIG-PP1_Cγ₁ or DIG-PP1_Cα. Solubilized PP1bp175 and PP1bp134 interact with PP1_C under native conditions, because they both (1) coeluted from size-exclusion and ion-exchange columns; (2) bound to microcystin-LR-Sepharose; and (3) coprecipitated using PP1_C antibodies. Trypsinolysis of the ≈600-kDa form of PP1 increased phosphorylase a phosphatase activity approximately fourfold, suggesting that interaction of PP1_C with these PP1bps modulates its activity. Thus, brain PP1 activity is likely targeted to the cytoskeleton, including postsynaptic densities, by isoform-selective binding of PP1_C to these targeting/regulatory subunits, contributing to the specificity of its physiological roles.     

Valence orbital response to conformers of n-butane

Individual outer valence orbital responses to rotations of the C–C central bond of butane (C₄H₁₀) are explored on the torsional potential energy surface. Orbital ionization energies, topologies and momentum distributions for the four most significant butane conformation are presented, as snapshots of the conformational variations. The analysis is based on quantum mechanically generated information from coordinate space and momentum space, a technique called dual space analysis (DSA). By comparison with experimental measurements of photo-electron spectra (PES) for energies and of electron momentum spectra (EMS) for energies and Dyson orbitals, we demonstrate that the individual outer valence orbitals of these conformers response differently to the rotations of the central C–C bond of n-butane. Orbital signatures of other higher energy conformations, such as orbitals la ₂ and 5a ₁ of conformation D (C_2v ), are identified. This finding indicates a co-existence of butane conformations, although the global minimum structure of anti-butane, A (C_2h ), is dominant. Orbital topology and electron charges redistribution during the transformation provide useful information on the chemical bonding and related chemical reactions.     

On the conformational dependence of the proton chemical shifts in nucleosides and nucleotides. II. Proton shifts in the ribose ring of purine nucleosides as a function of the torsion angle about the glycosyl bond

The variations of the ring current, the local diamagnetic susceptibility anisotropy and the polarization contributions to the chemical shift of the non exchangeable protons of the ribose ring of purine nucleosides are computed as a function of the torsion angle about the glycosyl bond, χ_CN. The results show that the ring current effect is relatively more important in the purines than in the pyrimidines. In addition, N₃ of purines has a local magnetic anisotropy effect similar to the one of the carbonyl group C₂O₂ of pyrimidine nucleosides. The experimental differences between the chemical shift of the ribose protons of purine nucleosides and of 8 substituted derivatives are discussed in relation to the theoretical variations.     

Rheology of synovial fluid

After a discussion of the role of synovial fluid as a joint lubricant, rheological measurements are described with both normal (healthy) synovial fluids and pathological ones. Shear stress and first normal stress difference are measured as a function of shear gradient to calculate the apparent shear viscosity eta 1 and the apparent normal viscosity psi 7 as well as an apparent shear modulus G'. It is found, that in case of diseased synoviae all rheological parameters deteriorate. Most significant changes are observed with the zero shear viscosity eta 0, the shear modulus G', and a characteristic time theta 1, which is the reciprocal of the critical shear rate Dc which determines the onset of shear thinning. The rheological deterioration of synovial fluids is explained in terms of solute structure, whereby a molecular mass of the backbone hyaluronic acid of at least 10(7) g.mol-1 is required for satisfactory function. A theory of the rheological performance of normal synovial fluid as well as its pathological deterioration is proposed.     

Conformational studies on polynucleotide chains. IV. Backbone structure of ribonucleic acids.

In preceding papers the energies associated with the internal rotations in the sugar–phosphate–sugar complex were described with an analytical potential consisting of a Lennard-Jones 6–12 term and an intrinsic torsional term and representing the best fit to a large number of energies computed with a quantum mechanical ab initio technique. The complex considered there (of 37 atoms and with the chemical formula C₁₀H₁₈O₈P) is repesentative of deoxyribonucleic acids. In this paper we apply our potential to evaluating the intramolecular energies of the 39-atom complex C₁₀H₁₈O₁₀P, representative of the ribonucleic acids. The potential energies for the internal rotations (considered independent from one another) and the energy maps for rotations about consecutive bonds of the backbone chain are critically compared, both with those obtained for the deoxy system and with those obtained from different theoretical approaches as available from literature. It is shown that, at least for certain combinations of the internal rotation angles, the choice of the starting geometry for the sugarphosphate–sugar molecule (bond lengths and valence angles) strongly affects the value of the computed energy. If a proper geometry is used, very low energies are predicted by our potential in correspondence of the sets of torsional angles found in various RNAs by x-ray crystallography.     

Characteristics and nature of the intermolecular interactions in boron-bonded complexes with carbene as electron donor: an <Emphasis Type="Italic">ab initio</Emphasis>, SAPT and QTAIM study

We report geometries, stabilization energies, symmetry adapted perturbation theory (SAPT) and quantum theory of atoms in molecules (QTAIM) analyses of a series of carbene–BX₃ complexes, where X = H, OH, NH₂, CH₃, CN, NC, F, Cl, and Br. The stabilization energies were calculated at HF, B3LYP, MP2, MP4 and CCSD(T)/aug-cc-pVDZ levels of theory using optimized geometries of all the complexes obtained from B3LYP/aug-cc-pVTZ. Quantitatively, all the complexes indicate the presence of B–C_carbene interaction due to the short B–C_carbene distances. Inspection of stabilization energies reveals that the interaction energies increase in the order NH₂ > OH > CH₃ > F > H > Cl > Br > NC > CN, which is the opposite trend shown in the binding distances. Considering the SAPT results, it is found that electrostatic effects account for about 50% of the overall attraction of the studied complexes. By comparison, the induction components of these interactions represent about 40% of the total attractive forces. Despite falling in a region of charge depletion with ∇² ρ _BCP >0, the B–C_carbene bond critical points (BCPs) are characterized by a reasonably large value of the electron density (ρ _BCP) and H_BCP <0, indicating that the potential energy overcomes the kinetic energy density at BCP and the B–C_carbene bond is a polar covalent bond.     

Effect of anisotropy of the bending rigidity on the supercoiling free energy of small circular DNAs

In principle, the supercoiling free energy of a small circular DNA will be enhanced by increasing the anisotropy of its bending potential at constant persistence length. The magnitude of this effect is investigated by Monte Carlo simulation using an extension of a previously proposed algorithm. The supercoiling free energy at 298 K is simulated for circular DNAs containing N = 100 bp with torsion constant α = 5.8 × 10^?12 dyne cm. persistence lengths P = 500 Å and 10,000 Å and a range of anisotropies of the bending potential from p = 1.0 to 16.0. The apparent torsion constants, reckoned from these supercoiling free energies by assuming an isotropic bending potential, are found to increase by less than 3% as the input anisotropy increases from 1.0 to 16.0. When P = 500 Å, the apparent torsion constant never rises significantly above the input value over the entire range of input anisotropies. When P = 10,000 Å, the apparent torsion constant rises only about 3% above the input value for anisotropies ρ = 8.0 and 16.0. Evidently, anisotropy of the bending potential cannot account for the fact that the torsion constants reported for small circular DNAs exceed those reported for longlinear DNAs by a factor of 1.6 or more. © 1995 John Wiley & Sons, Inc.