Infrared and vibrational CD spectra of partially solvated alpha-helices: DFT-based simulations with explicit solvent

Theoretical simulations are used to investigate the effects of aqueous solvent on the vibrational spectra of model alpha-helices, which are only partly exposed to solvent to mimic alpha-helices in proteins. Infrared absorption (IR) and vibrational circular dichroism (VCD) amide I' spectra for 15-amide alanine alpha-helices are simulated using density functional theory (DFT) calculations combined with the property transfer method. The solvent is modeled by explicit water molecules hydrogen bonded to the solvated amide groups. Simulated spectra for two partially solvated model alpha-helices, one corresponding to a more exposed and the other to a more buried structure, are compared to the fully solvated and unsolvated (gas phase) simulations. The dependence of the amide I spectra on the orientation of the partially solvated helix with respect to the solvent and effects of solvation on the amide I' of 13C isotopically substituted alpha-helices are also investigated. The partial exposure to solvent causes significant broadening of the amide I' bands due to differences in the vibrational frequencies of the explicitly solvated and unsolvated amide groups. The different degree of partial solvation is reflected primarily in the frequency shifts of the unsolvated (buried) amide group vibrations. Depending on which side of the alpha-helix is exposed to solvent, the simulated IR band-shapes exhibit significant changes, from broad and relatively featureless to distinctly split into two maxima. The simulated amide I' VCD band-shapes for the partially solvated alpha-helices parallel the broadening of the IR and exhibit more sign variation, but generally preserve the sign pattern characteristic of the alpha-helical structures and are much less dependent on the alpha-helix orientation with respect to the solvent. The simulated amide I' IR spectra for the model peptides with explicitly hydrogen-bonded water are consistent with the experimental data for small alpha-helical proteins at very low temperatures, but overestimate the effects of solvent on the protein spectra at ambient temperatures, where the peptide-water hydrogen bonds are weakened by thermal motion.     

Synthesis and characterization of solvated trifluoroacetate alkaline earth derivatives

The synthesis and characterization of the trifluoroacetic acid (H-TFA) derivatives of a series of alkaline earth congeners was undertaken through the dissolution of the alkaline earth (A^E) metal in H-TFA. After drying, the resulting reaction powders were independently crystallized from Lewis basic solvents [pyridine (py) or tetrahydrofuran (THF)] as diverse A^E-TFA derivatives. For the smallest cation, an octahedrally bound monomer Mg(TFA)₂(py)₄ (1) was isolated, wherein the TFA ligands were all terminally (TFA) bound. The remaining compounds were found to adopt polymeric structures with: only bridging (μ-TFA) ligands for {[Ca₂(μ-TFA)₃(THF)₄](μ-TFA)}_n (2); a mixture of μ-TFA and chelating bridging (μ_c-TFA) ligands in {[(μ-TFA)₂Sr(μ_c-TFA)][H-py]py}_n (3); and only μ_c-TFA ligands for {[Ba(μ_c-TFA)₂(μ_c-TFA)(py)][H-py]}_n (4) structure. The later two structures were solved with a pyridinium salt located in the lattice. The trend observed for the TFA ligand was that as the cation increases in size, the ligands transform from bridging to chelating bridging due to the increased coordination sphere of the metals. Elemental analyses, solid-state, and solution multinuclear NMR, and FTIR data confirm the bulk powders were consistent with the X-ray structures.     

Germanium nanoparticles from solvated atoms: synthesis and characterization

Germanium nanoparticles were synthesized by the chemical liquid deposition method (CLD) in which the Ge atoms, produced resistively, were co-deposited with 2-propanol, acetone and tetrahydrofurane vapors to obtain colloidal dispersions. The colloidal dispersions were characterized by UV-vis spectrophotometry, transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED) and Infrared Spectroscopy (FTIR) techniques. The Germanium colloids are, in general, kinetically unstable. Strong absorption bands in the UV region suggest that nanoparticles obtained by this procedure exhibit quantum confinement. In the Ge colloids, the particle size distribution is highly sensitive to concentration change. For example, the TEM measurements revealed for the Ge-2-propanol colloid, particle sizes close to 3 nm for a concentration of 10^–3 M and 30 nm for a concentration of 10^–2 M. The HRTEM and SAED showed the high crystallinity of the nanoparticles, and it was possible to observe the typical lattice spaces of a diamond cubic Ge structure. The FTIR studies revealed the Ge-organic nature of the particles surface. Mechanisms and structures have been proposed for surface reactions.     

Mixed monolayers of poly-alanine and lipids at the air-water interface

Summary The mixed monolayers of poly-alanine + stearyl alcohol and poly-alanine + cholesterol were studied at the air-water interface. In the mixed monolayers the surface pressure-area isotherms showed three collapse states. The first and the third collapse pressures were identical in magnitude with the collapse pressures of pure components. The intermediate collapse pressure in the poly-alanine + stearyl alcohol was found to be ca. 5 dyne/cm higher than that was observed in the poly-alanine + cholesterol system. Further, the mixed films in both systems were found to show no deviation from the ideality rule. The magnitude o f the intermediate collapse state is shown to be related to the van der Waals forces present in the lipid films.With 6 figures     

Structural stability of the solvated cellulose IIII crystal models: a molecular dynamics study

Molecular dynamics (MD) simulations of cellulose III_I crystal models have been carried out. The crystal models were composed by either 24 or 48 cellooligomers consisting of either 20 or 40 residues and were surrounded by waters in a periodic boundary box. Two base plane types differing in a constituent crystal lattice plane, (0 −1 0) × (0 1 0) and (1 0 0) × (0 1 0), were additionally considered. Among the resulting eight crystal models, an overall structure conversion was observed for the seven models. The final structures had a triclinic-like chain arrangement involving one-quarter staggering chains with respect to its axis. The successive, local transformation involving cooperative bends in cellooligomers was observed during the structure conversion. Only the 48 × 20-mer model having the (0 −1 0) lattice plane retained the original crystal structure throughout a 2.5-ns simulation. The MD simulations with an implicit solvent system and a vacuum system were also performed to asses a solvent effect on the structure conversion.     

The elasticity of alpha-helices

The elasticity of alpha-helices is examined using equilibrium molecular-dynamics simulations. From the statistics of curvatures and twists, we compute the elastic moduli of several representative alpha-helices, both in the presence and absence of aqueous solvent. We discover that the bending modulus (persistence length) of the helices is independent of the amino-acid sequence, although helices in water are slightly softer than in vacuum. The response of the helices under the action of an external force is also computed and compared with continuum mechanics predictions. Within the time scale of our simulation, we show that the properties of alpha-helices are well reproduced by an elastic and isotropic rod. The persistence length (bending modulus) of most alpha-helices in water or vacuum is approximately 100 nm, roughly twice that of DNA.     

The prediction of amphiphilic alpha-helices

A number of sequence-based analyses have been developed to identify protein segments, which are able to form membrane interactive amphiphilic alpha-helices. Earlier techniques attempted to detect the characteristic periodicity in hydrophobic amino acid residues shown by these structure and included the Molecular Hydrophobic Potential (MHP), which represents the hydrophobicity of amino acid residues as lines of isopotential around the alpha-helix and analyses based on Fourier transforms. These latter analyses compare the periodicity of hydrophobic residues in a putative alpha-helical sequence with that of a test mathematical function to provide a measure of amphiphilicity using either the Amphipathic Index or the Hydrophobic Moment. More recently, the introduction of computational procedures based on techniques such as hydropathy analysis, homology modelling, multiple sequence alignments and neural networks has led to the prediction of transmembrane alpha-helices with accuracies of the order of 95% and transmembrane protein topology with accuracies greater than 75%. Statistical approaches to transmembrane protein modeling such as hidden Markov models have increased these prediction levels to an even higher level. Here, we review a number of these predictive techniques and consider problems associated with their use in the prediction of structure / function relationships, using alpha-helices from G-coupled protein receptors, penicillin binding proteins, apolipoproteins, peptide hormones, lytic peptides and tilted peptides as examples.     

Synthetic non-peptide mimetics of alpha-helices

Proteins in nature fold into native conformations in which combinations of peripherally projected aliphatic, aromatic and ionic functionalities direct a wide range of properties. Alpha-helices, one of the most common protein secondary structures, serve as important recognition regions on protein surfaces for numerous protein-protein, protein-DNA and protein-RNA interactions. These interactions are characterized by conserved structural features within the alpha-helical domain. Rational design of structural mimetics of these domains with synthetic small molecules has proven an effective means to modulate such protein functions. In this tutorial review we discuss strategies that utilize synthetic small-molecule antagonists to selectively target essential protein-protein interactions involved in certain diseases. We also evaluate some of the protein-protein interactions that have been or are potential targets for alpha-helix mimetics.     

Structural characterization of magnetoferritin

1. Download : Download full-size image

     

Structural characterization of ZnLiNbO4

The structure of ZnLiNbO₄ crystals grown directly from the stoichiometric melt by the Laser Heated Pedestal Growth technique has been determined by X-ray diffraction. ZnLiNbO₄ crystallizes in the space group P4₁22 (n^o 91) with a=6.0818(9) Å c=8.3818(17) Å and Z=4. The crystal structure is that of an ordered type of a tetragonal spinel with Nb and Li ions in octahedral environment and Zn ions in tetrahedral position.     

Pyridine solvated dioxouranium complex with salen ligand: Synthesis,characterization and luminescence properties

A new derivative of dioxouranium(VI) salen complex, [UO2(L)(pyridine)], where [L = N,N′-Bis(2-hydroxybenzylidene)-2,2-dimethyl-1,3-propanediamine] is synthesized and characterized by elemental analysis (C, H, N), FT-IR, ESI-MS spectrometry, UV/Vis, fluorescence, ¹H and ¹³C NMR spectroscopy and thermal gravimetric (TG) study. Furthermore, the single crystal X-ray diffraction measurements of the complex were carried out at 100 and 273 K. The crystal structure measurements revealed that the complex has distorted pentagonal bipyramidal geometry with uranium atom located at the centre and bonded to two phenoxy oxygen and two azomethine nitrogen in tetradenate fashion and one nitrogen from pyridine making it seven coordinated. In addition, the photoluminescence property of the complex was also recorded.     

Time-resolved spectroscopy of solvated electrons

The theory of time-dependent transient spectra of solvated electrons is developed. It is shown that the evolution of the spectral line centre reproduces the time dependence of the classical correlation function of the random process of electronic energy level fluctuations. The results of this investigation are compared with experiment.     

Spectral moments of solvated electrons

A moment theory analysis is performed on the optical absorption spectra of surplus electrons localized in various media. The deduced attributes of the excess particle are compared with those obtained by a perturbation treatment of the exact ground state solution of a currently popular model potential for the species. Several frequency dependent observables are evaluated and a source of inadequacy in the current theory, the presence of a Coulomb tail, is revealed.     

Solid-phase synthesis of hydrogen-bond surrogate-derived alpha-helices

[reaction: see text] This report describes the solid-phase synthesis of hydrogen-bond surrogate-derived artificial alpha-helices by a ring-closing metathesis reaction. From a series of metathesis catalysts evaluated for the synthesis of these helices, the Hoveyda-Grubbs catalyst was found to afford high yields of the macrocycle irrespective of the peptide sequence.     

Helix forming tendency of valine substituted poly-alanine: a molecular dynamics investigation

In this study, classical molecular dynamics simulations have been carried out on the valine (guest) substituted poly alanine (host) using the host-guest peptide approach to understand the role of valine in the formation and stabilization of helix. Valine has been substituted in the host peptide starting from N terminal to C terminal. Various structural parameters have been obtained from the molecular dynamics simulation to understand the tolerance of helical motif to valine. Depending on the position of valine in the host peptide, it stabilizes (or destabilizes) the formation of the helical structure. The substitution of valine in the poly alanine at some positions has no effect on the helix formation (deformation). It is interesting to observe the coexistence of 3 10 and alpha-helix in the peptides due to the dynamical nature of the hydrogen bonding interaction and sterical interactions.     

Oblique orientated alpha-helices and their prediction

Oblique orientated alpha-helices possess hydrophobicity gradients, which allow the parent alpha-helices to penetrate the membrane at a shallow angle, thereby destabilising membrane lipid organisation and promoting a range of biological processes. These alpha-helices occur in a variety of membrane interactive proteins and a number of techniques have been developed to guide their identification using sequence data alone. Hydrophobicity profiling, which provides a one-dimensional analysis of sequence data, identified only 30% of known tilted peptides in a control dataset and was thus of limited predictive use. In contrast, extended hydrophobic moment plot methodology and amphipilic profiling which take residue distribution into account and provide two-dimensional analysis of primary structural data, were found to be good indicators of tilted peptide structure. Amphiphilic profiling identified 67% of tilted peptides in the control dataset and showed that potentially, approximately 40% of transmembrane alpha-helices possess tilted peptide structure. However, it has been shown that extending these simple methods to take into account the three-dimensional spatial distribution of residues gives no clear additional benefit to identifying tilted peptides.     

Compton profiles of solvated electrons

The importance of applying a variety of experimental techniques to unravel the nature of solvated electrons is emphasized. Compton profiles are evaluated for these species from a range of models. Some comparisons are made with positron annihilation studies.