Rigid Helix Research Articles

The solution structure of the active domain of CAP18 — a lipopolysaccharide binding protein from rabbit leukocytes

We have employed the circular dichroism (CD) technique to characterize the solution structure of CAP18 106–137, a lipopolysaccharide (LPS) binding, antimicrobial protein, and its interaction with lipid A. Our results revealed that CAP18 106–137 may exist in at least three lipid A concentration-dependent, primarily helix conformations. The ‘model’ structure of CAP18 106–137 in 30% (v/v) TFE, determined by nuclear magnetic resonance (NMR) technique, was found to be a complete and very rigid helix. In this conformation, the cationic and hydrophobic groups of CAP18 106–137 are separated into patches and stripes in such a way that it can favorably interact with lipid A through either coulombic interaction with the diphosphoryl groups or hydrophobic interaction with the fatty acyl chains.

α‐Helix‐forming propensities in peptides and proteins

Much effort has been invested in seeking to understand the thermodynamic basis of helix stability in both peptides and proteins. Recently, several groups have measured the helix-forming propensities of individual residues (Lyu, P.C., Liff, M.I., Marky, L.A., Kallenbach, N.R. Science 250:669-673, 1990; O'Neil, K.T., DeGrado, W.F. Science 250:646-651, 1990; Padmanabhan, S., Marqusee, S., Ridgeway, T., Laue, T.M., Baldwin, R.L. Nature (London) 344:268-270, 1990). Using Monte Carlo computer simulations, we tested the hypothesis that these differences in measured helix-forming propensity are due primarily to loss of side chain conformational entropy upon helix formation (Creamer, T.P., Rose, G.D. Proc. Natl. Acad. Sci. U.S.A. 89:5937-5941, 1992). Our previous study employed a rigid helix backbone, which is here generalized to a completely flexible helix model in order to ensure that earlier results were not a methodological artifact. Using this flexible model, side chain rotamer distributions and entropy losses are calculated and shown to agree with those obtained earlier. We note that the side chain conformational entropy calculated for Trp in our previous study was in error; a corrected value is presented. Extending earlier work, calculated entropy losses are found to correlate strongly with recent helix propensity scales derived from substitutions made within protein helices (Horovitz, A., Matthews, J.M., Fersht, A.R. J. Mol. Biol. 227:560-568, 1992; Blaber, M., Zhang, X.-J., Matthews, B.M. Science 260:1637-1640, 1993). In contrast, little correlation is found between these helix propensity scales and the accessible surface area buried upon formation of a model polyalanyl alpha-helix. Taken in sum, our results indicate that loss of side chain entropy is a major determinant of the helix-forming tendency of residues in both peptide and protein helices.

On the intrinsic viscosity of anionic and nonionic rodlike polysaccharide solutions

AbstractThe ionic strength dependence of intrinsic viscosity as a function of molecular weight was observed substantially for the anionic xanthan polyelectrolyte, while the intrinsic viscosity of nonionic schizophyllan does not change with ionic strength. Ultrasonic degradation was applied as the best mean of obtaining polymer fractions of different molecular weights. It is true, as expected, that schizophyllan has a more rigid triple helix backbone than that of xanthan. As the molecular weight increases, the extension coefficient ε of the xanthan chain with ionic strength is found empirically to increase by order 1,48 of molecular weight. Using the Yamakawa‐Fujii theory for worm‐like chains, both the persistence length q and the contour length Lc were determined from the best fit of the experimental data of intrinsic viscosity for different ionic strengths to the theoretical curves. The stiffness parameter was established from the ratio of the Kuhn statistical segment length (i. e., twice the persistence length) to the contour length. As the molecular weight decreases, stiff chains of short degraded xanthan become rodlike, while they become gradually worm‐like with increasing molecular weight. It also can be seen that the chain stiffness depends on the ionic strength.

Combination of Neutron Scattering and Molecular Dynamics to Determine Internal Motions in Biomolecules

Abstract The forms and frequencies of atomic dynamics on the pico- and nanosecond timescales are accessible experimentally using incoherent neutron scattering. Molecular dynamics simulations cover the same space and time domains and neutron scattering intensities can be calculated from the simulations for direct comparison with experiment. To illustrate the complementarity of neutron scattering and molecular dynamics we examine measured and simulation-derived elastic incoherent scattering profiles from myoglobin and from the crystalline alanine dipeptide. Elastic incoherent scattering gives information on the geometry of the volume accessible to the atoms in the samples. The simulation-derived dipeptide elastic scattering profiles are in reasonable accord with experiment, deviations being due to the sampling limitations in the simulations and experimental detector normalisation procedures. The simulated dynamics is decomposed, revealing characteristic profiles due to rotational diffusional and translational vibrational motions of the methyl groups. In myoglobin, for which the timescale of the simulation matches more closely that accessible to the experiment, good agreement is seen for the elastic incoherent structure factor. This indicates that the space sampled by the hydrogen atoms in the protein on the timescale <100 ps is well represented by the simulation. Part of the helix atom fluctuations can be described in terms of rigid helix motions.

Picosecond timescale rigid-helix and side-chain motions in deoxymyoglobin.

The contribution of rigid-body motions to the atomic trajectories in a 100 ps molecular dynamics simulation of deoxymyoglobin is examined. Two types of rigid-body motions are considered: one in which the helices are rigid units and one in which the side-chains are rigid units. Using a quaternion-based algorithm, fits of the rigid reference structures are made to each time frame of the simulation to derive trajectories of the rigid-body motions. The fitted trajectories are analysed in terms of atomic position fluctuations, mean-square displacements as a function of time, velocity autocorrelation functions and densities of states. The results are compared with the corresponding quantities calculated from the full trajectory. The relative contribution of the rigid helix motions to the helix atom dynamics depends on which quantity is examined and on which subset of atoms is chosen; rigid-helix motions contribute 86% of the rms helix backbone atomic position fluctuations, but 30% of the helix atom (backbone and side-chain) mean square displacements and only 1.1% of total kinetic energy. Only very low-frequency motions contribute to the rigid-helix dynamics; the rigid-body analysis allows characteristic rigid-helix vibrations to be identified and described. Treating the side-chains as rigid bodies is found to be an excellent approximation to both their diffusive and vibrational mean-square displacements: 96% of side-chain atom mean-square displacements originate from rigid side-chain motions. However, the errors in the side-chain atomic positional fits are not always small. An analysis is made of factors contributing to the positional error for different types of side-chain.

Determination of the molecular dynamics of alamethicin using carbon-13 NMR: implications for the mechanism of gating of a voltage-dependent channel

Alamethicin is a channel-forming peptide antibiotic that produces a highly voltage-dependent conductance in planar bilayers. To provide insight into the mechanisms for its voltage dependence, the dynamics of the peptide were examined in solution using nuclear magnetic resonance. Natural-abundance 13C spin-lattice relaxation rates and 13C-1H nuclear Overhauser effects of alamethicin were measured at two magnetic field strengths in methanol. This information was interpreted using a model-free approach to obtain values for the overall correlation times as well as the rates and amplitudes of the internal motions of the peptide. The picosecond, internal motions of alamethicin are highly restricted along the peptide backbone and indicate that it behaves as a rigid helical rod in solution. The side chain carbons exhibit increased segmental motion as their distance from the peptide backbone is increased; however, these motions are not unrestricted. Methyl group dynamics are also consistent with the restricted motions observed for the backbone carbons. There is no evidence from these dynamics measurements for a hinged motion of the peptide about proline-14. Alamethicin appears to be slightly less structured in methanol than in the membrane; as a result, alamethicin is also expected to behave as a rigid helix in the membrane. This suggests that the gating of this peptide involves changes in the orientation of the entire helix, rather than the movement of a segment of the peptide backbone.

The design and construction of synthetic protein mimics

Abstract

Theory of electrostriction of liquid-crystalline blue phases I and II.

For the cubic lattices of the liquid-crystalline blue phases I and II electrostriction has been observed recently, i.e., a distortion of the crystal by an electric field in quadratic order. Here we investigate the characterizing fourth-order electrostriction tensor. Because electrostriction results from a competition between electric and elastic forces, the tensor is the quotient of the elasto-optic and the elastic tensor. The latter are derived from the Landau--de Gennes theory of phase transitions in liquid crystals within the model of rigid helices and are expressed as functionals of the alignment tensor for the undistorted system. Comparison is made with experimental data. The limitations of the model of rigid helices are discussed.

Ion transport in a model gramicidin channel. Structure and thermodynamics

The potential of mean force for Na+ and K+ ions as a function of position in the interior of a periodic poly(L,D)-alanine model for the gramicidin beta-helix is calculated with a detailed atomic model and realistic interactions. The calculated free energy barriers are 4.5 kcal/mol for Na+ and 1.0 kcal/mol for K+. A decomposition of the free energy demonstrates that the water molecules make a significant contribution to the free energy of activation. There is an increase in entropy at the transition state associated with greater fluctuations. Analysis reveals that the free energy profile of ions in the periodic channel is controlled not by the large interaction energy involving the ion but rather by the weaker water-water, water-peptide and peptide-peptide hydrogen bond interactions. The interior of the channel retains much of the solvation properties of a liquid in its interactions with the cations. Of particular importance is the flexibility of the helix, which permits it to respond to the presence of an ion in a fluidlike manner. The distortion of the helix is local (limited to a few carbonyls) because the structure is too flexible to transmit a perturbation to large distances. The plasticity of the structure (i.e., the property to deform without generating a large energy stress) appears to be an essential factor in the transport of ions, suggesting that a rigid helix model would be inappropriate.

Nuclear magnetic relaxation of α‐13C nuclei of helical poly(γ‐hexyl‐L‐glutamate) and poly(γ‐benzyl‐L‐glutamate)

AbstractSpin‐lattice relaxation times (T1), spin‐spin relaxation times (T2), and nuclear Overhauser enhancements (NOE), at 75.5 MHz are reported for α‐13C nuclei of poly (γ‐benzyl‐L‐glutamate) in deuterated dimethylformamide at 60°C and of poly(γ‐hexyl‐L‐glutamate) in cyclohexanone at 48 and 79°C. It is shown that for molecular weights above 105, the polypeptides cannot be considered as essentially rigid helices with internal librational motions; additional backbone flexing motions contribute to the relaxation behavior.

A harmonic oscillator model of the conformationally flexible helical polymeric molecules

The approach of the persistence vector to its asymptotic limit can be characterized by the average projection of a unit vector along the last bond onto a unit vector along the first bond. The behavior of this projection has been examined in simple, predominantly helical chains in which limited flexibility is introduced by either of two devices: occurrence in an average way of a configuration much different from that required for helix propagation, and use of a square-well potential centered at the dihedral angle utilized in a rigid helix. The manner in which flexibility is introduced determines the behavior of the angular frequency as well as the relative decay rates for oscillations and the midpoint about which oscillations occur.

87Rb + spin relaxation in enzymically purified and in untreated iota-carrageenan

The temperature dependences of the transverse ( R 2) and longitudinal ( R 1) n.m.r. relaxation rates of 87Rb + in aqueous 5% iota-carrageenan have been compared with similar data for a sample purified by treatment with kappa-carrageenase. In each sample, the relaxation rates were sensitive to the conformation (helix or random coil). In the intact sample, the small (⩽ 5%) fraction of kappa-carrageenan (which, in its helical state, specifically binds rubidium ions) was solely responsible for the pronounced line-broadening that has been observed hitherto for 87Rb in iota-carrageenan gels. In the purified sample, the effects on the relaxation of 87Rb induced by iota-carrageenan are similar to those found in comparable systems in the absence of site-binding of the ions. Thus, there was a modest enhancement of the relaxation with R 1 ≈ R 2 for the flexible coil conformation and a comparably larger effect, with significant contributions from dynamic processes on the time-scale of the inverse resonance frequency or longer, for the thicker, more highly charged and rigid helix conformation of iota-carrageenan.

Order–disorder transitions in Langmuir–Blodgett films. IV. Structure of [F(CF2)8(CH2)1COO−]2 Cd2+ multilayers at ambient and elevated temperatures

Langmuir–Blodgett multilayered (6–12) films of a semifluorinated fatty acid, F(CF2)8(CH2)10COOH, have been deposited on transmission and reflection substrates and investigated using polarized infrared (IR) spectroscopy. The spectra revealed that the cadmium salt of this fatty acid was transferred and not the acid itself. Unlike its hydrocarbon analog, [F(CF2)8(CH2)10COO−]2 Cd2+ is not oriented normal to the surface but is inclined due to the packing constraints dictated by the considerably larger cross section of the fluorocarbon part of the molecule. At elevated temperatures, the orientation of the fluorocarbon chain is observed to change and this has been attributed to disordered conformations preferentially introduced in the hydrocarbon portion of the molecule due to its inherent flexibility relative to the rigid fluorocarbon helix.

Enantiomer-selective polymerization of racemic phenyl-2-pyridyl-o-tolylmethyl methacrylate controlled by a rigid helix

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnantiomer-selective polymerization of racemic phenyl-2-pyridyl-o-tolylmethyl methacrylate controlled by a rigid helixEiji Yashima, Yoshio Okamoto, and Koichi HatadaCite this: Macromolecules 1988, 21, 3, 854–855Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://doi.org/10.1021/ma00181a050RIGHTS & PERMISSIONSArticle Views187Altmetric-Citations24LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (288 KB) Get e-Alerts Get e-Alerts

Depth-dependent fluorescent quenching of a tryptophan residue located at defined positions on a rigid 21-peptide helix in liposomes

Five lipophilic 21-peptide analogs of the potential-dependent pore-former, alamethicin, were synthesized bearing tryptophan residues at the position 1, 6, 11, 16 and 21 on a long, conformationally rigid, α-helix. The α-helical conformation was induced and stabilized using the sequential oligomers (Ala-Aib-Ala-Aib-Ala) n as analyzed by CD and NMR. The partitioning of the N- t-butoxycarbonyl 21-peptide methyl esters and the N-terminally deprotected α-helices was followed by fluorescence enhancement in phospholipid bilayer vesicles. Quenching experiments were performed by titrating with n-doxyl stearic acids bearing the nitroxide label at positions 5, 7, 10, 12 and 16. This well-defined system revealed that the N- and C-terminal tryptophan residues become situated in the hydrophilic region. Tryptophan at position 11 was found in the lipophilic core, whereas the tryptophan at positions 6 and 16 were localized at Intermediate depths of the lipid membrane. Therefore, the helices span the lipid bilayer with their long axis normal to the membrane surface.

Correlation between the antitumor activity of a polysaccharide schizophyllan and its triple-helical conformation in dilute aqueous solution

Eight samples of a polysaccharide schizophyllan ranging in weight-average molecular weight Mw (in water) from 5 x 10(3) to 1.3 x 10(5) were prepared and their antitumor activity (expressed in terms of the tumor inhibition ratio) against Sarcoma 180 ascites, intrinsic viscosities [eta], and gel-filtration chromatograms in aqueous solution were determined. The tumor inhibition ratio was essentially unity for samples with Mw higher than 9 x 10(4), but reduced to zero or even to a negative value when Mw was lower than 10(4). The [eta] data combined with the chromatographic data showed that above Mw approximately 9 x 10(4) the predominant species of schizophyllan in aqueous solution is the previously found rigid triple helix, whereas below Mw approximately 9 x 10(4) both triple helices and single chains coexist in the solution and the fraction of triple helices decreases monotonically to zero as Mw is decreased to 5 x 10(3). From these findings it was concluded that the antitumor potency of schizophyllan in water is related to the amount of triple helices relative to that of single chains.

Propulsion of micro-organisms by three-dimensional flagellar waves

The hydrodynamic effects of non-uniformities in cross-section and wavelength of three-dimensional flagellar waveforms are investigated. Estimates of propulsive velocity obtained by the use of mean constant wave parameters are close to the more precise calculations except where the wavelength varies more than twofold during wave propagation. Energy expenditures against external viscous forces are appreciably greater than the estimates based on mean wave parameter assumptions. Rotation of an inert head attached to a flagellum contributes a significant proportion of the total power dissipation. Energy requirements of an individual bull spermatozoon are greater than previous estimates. There is little difference between the energy supplies necessary to propel bacteria by rotating rigid flagellar helices or by propagation of helical waves.

Statistics of stiff chain molecules: II. The mean square radius of gyration of semiflexible helices

AbstractA simple chain model for semiflexible helices, defined by the pitch height, the number of residues per turn and a certain flexibility, is suggested. In this model, the coordinate system is chosen such that, in the limit of a rigid and perfect helix, the z‐axis coincides with the helix axis. Owing to its flexibility, the moving helix axis is allowed to perform random fluctuations in the x and y directions within certain limits. Analytic expressions are derived for the mean square end‐to‐end distance and for the mean square radius of gyration as functions of the degree of polymerisation through the use of generating functions. There appear three essential roots of a cubic equation, the largest of which is determined by the flexibility of the helix.

The physical properties of polyisocyanates in solution

Electric birefringence measurements have been made on four samples of poly-n-butyl isocyanate in three solvents. The value of M W/ M N for three of the samples was 1·2. A description of the apparatus and of its use with both alternating and pulsed direct current electric fields is given. The method has been used to obtain molecular relaxation times and dipole moments. These data have been analysed, together with the results of dielectric experiments reported in the literature, in terms of both rigid helices and weakly bending helices. The results indicate that flexibility is encountered for molecular weights in excess of 5 × 10 4. This is somewhat lower than had previously been reported from other relaxation experiments. Below this molecular weight, the observed molecular relaxation times, which were associated with an end-over-end rotation due to the helices having a permanent dipole moment along their helical axis, were related to a number average molecular weight. Data were consistent with a helix monomer projection length of 1·3 Å and a diameter of 11 Å. In the range 5 × 10 4 < M N < 10 5 , the data have been interpreted in terms of Hearst's recent theory for weakly bending rods. These results were consistent with the worm-like chain model, used to interpret the data for molecular weights in excess of 100,000. It was shown that the assignment of a specific persistence length was unreliable even for molecular weights as high as 5 × 10 5. The study demonstrates the merits and sensitivity of the electric birefringence method. It is the first time that the “double frequency” component of the birefringence, which is generated when alternating fields are applied to the solutions, has been detected and used to determine molecular parameters for a synthetic polymer.

Helix antenna for spacecraft

This paper describes the development and performance of a light-weight, high-gain, high-efficiency, rigid helix antenna and discusses a light-weight deployable helix antenna.The weight of the rigid helix was 016 kg (0.35 lb) and had a measured gain of 16.5 dB at 2.3 GHz. The estimated weight of the deployable helix is 0.06 kg (0.13 lb). Such antenna elements can be used for phased arrays for spacecraft.