bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualization of the nature of protein folding by a study of a distance constraint approach in two‐dimensional models
Authors: Wako Hiroshi , Scheraga Harold A. 
Published: December 2004

AbstractA distance constraint approach is applied to two‐dimensional models of proteins in order to visualize the nature of protein folding and to examine the relative roles of different ranges of interaction. Three different native structures (I, II, and III) are considered; they have two different kinds of residues, viz., hydrophobic and hydrophilic, and different sequences of these residues. We examine how the distance constraint approach functions in the prediction of protein folding when we know the sequence of the residues, the (fixed) bond lengths, the mean distances between residues i and i + 2, and i and i + 3, and the mean distances for hydrophobic–hydrophobic, hydrophobic–hydrophilic, and hydrophilic–hydrophilic contacts between residues i and i + j, where j ≥ 4. This approach involves optimization of an object function with respect to 98 variables and is not free of the multiple‐minimum problem. The optimization is always terminated if the chain is entangled and/or the segments (residues) are packed too compactly to move. In order to escape from such situations and to take the excluded‐volume effect into account, a Monte Carlo method is used after the optimization is trapped in local minima. Success in the prediction of folding is found to depend on the starting conformations and on the native conformations. Fair success is obtained in predicting the helix‐like structure in protein I and the overall structure of protein III, but not the β‐like structures of proteins I and II. Insofar as the prediction of the structure of protein III is reasonable, it appears that some sequences of residues produce greater constraints on their conformations than others, if one considers only the hydrophobic and hydrophilic nature of the residues. These results imply that, in the folding of real proteins in three dimensions, the competition for hydrophobic (and hydrophilic) residues for inside (outside) positions in the molecule probably constitutes a necessary but not a sufficient condition to form and stabilize the native structure. The failure to predict the structure of protein II, and part of that of protein I, suggests that there are two types of long‐range interactions. One (which we considered here) is nonspecific (i.e., is defined only in terms of contacts between residues of the same or different polarity) and acts at any stage of protein folding; the other (which we did not consider here) is a specific interaction between residues in pairs and contributes only when the residues in the specific pair take on the native conformation. Presumably, incorporation of such specific long‐range interactions, together with the nonspecific ones, is necessary for successful protein folding, using the distance constraint approach.
Interactions of molecules with nucleic acids. VI. Computer design of chromophoric intercalating agents
Authors: Miller Kenneth J. , Newlin Donald D. 
Published: December 2004

AbstractThe mode of action of many antitumor agents entails the inhibition of nucleic acid synthesis. Because many of the drugs can intercalate, it is assumed that intercalation is an important step in the mechanism of biological activity. As intercalants contain a planar chromophore as an ingredient essential for intercalation, chromophores that should fit into DNA are desired. This is the main theme of this investigation. Binding to DNA of fundamental moieties, protonated pyridine, aniline, phenol, quinone, and 4H‐thiopyran‐4‐one, is studied to determine their optimum placement in DNA. The optimum orientations for each moiety are superimposed to form polyaromatic systems that can intercalate in a manner in which functional groups on these chromophores are oriented as in the moieties themselves. Ideal intercalants proposed contain three and four fused ring system, have protonated ring nitrogen atoms located to maximize the electrostatic interactions with DNA, hydroxy and amino groups that can hydrogen bond to the OII and O5′ phosphate backbone atoms, and carbonyl and sulfur groups in the central position of the ring system to provide variations in the chromophore and to interact with the relatively positive region in the intercalation site. The optimum orientation occurs when the chromophore and the base pairs overlap to the maximum extent. The ideal intercalants are fundamentally of the type: magnified image
25Mg‐nmr investigations of the magnesium ion–DNA interaction
Authors: Rose D. Murk , Polnaszek C. F. , Bryant R. G. 
Published: December 2004

Abstract25Mg‐nmr data are reported that address the nature of the magnesium ion–DNA interaction. It is found that competitor ions such as calcium, mercury, zinc, and cobalt ions are not effective in competing for all of the magnesium ion–DNA interaction that is reported by the 25Mg‐nmr spectrum. The temperature dependence of the 25Mg‐nmr spectrum in DNA solution studied at high concentrations of competitor ion indicates that the chemical‐exchange lifetime of the magnesium ions at DNA binding sites makes a major contribution to the 25Mg‐nmr line width. However, the activation parameters are not consistent with the temperature dependence of either transport properties or chemical exchange with phosphate groups alone, but are consistent with a sum of at least two processes that provide opposing contributions to the 25Mg‐nmr relaxation. It is also shown that the non‐Lorentzian character of the 25Mg‐nmr line previously reported is consistent with the effect of an incompletely averaged static nuclear electric quadrupole interaction and/or an exchange process that is slow with respect to the magnitude of this interaction. Because the concentrations employed in these experiments are high, the present data do not provide a direct or critical test of the electrostatic theories of ion–polyelectrolyte interaction. The present data do demonstrate, however, that such theories alone are insufficient as a basis for understanding the 25Mg‐nmr data.
Stable cruciform formation at inverted repeat sequences in supercoiled DNA
Authors: Benham Craig J. 
Published: December 2004

AbstractThis paper analyzes equilibrium superhelical cruciform formation in a topologial domain of DNA containing inverted repeat sequences. The cruciform conformation is shown to be stable when the molecule is sufficiently negatively supercoiled but not when it is positively supercoiled. For a particular sequence containing a single inverted repeat, onset of stability occurs at a degree of negative superhelicity that depends critically on the number of base pairs separating the repeat copies. The free energy associated with the stable cruciform state is constant, independent of the degree of superhelicity, up to the point where the complete inverted repeat participates in the cruciform. In contrast, the free energy of the alternative, unextruded state grows approximately quadratically with the superhelical deformation. Therefore, a degree of negative supercoiling occurs at which the cruciform state becomes energetically favored. The equilibrium properties of this cruciform extrusion transition vary with segment length, the positions and sizes of the inverted repeats involved, environmental conditions, and the degree of superhelicity imposed. In a segment containing multiple repeats, both tandem and inverted, of one or more sequences, the pattern of cruciforms that form is dependent on superhelicity in a complex way. Specific cruciforms may occur at equilibrium only in narrow ranges of superhelicity, their reabsorption being coupled to the extrusion of others.
Stereospecific oxidation of ascorbic acid by chiral association complexes between polypeptides and iron(III) chelate ions
Authors: Barteri M. , Pispisa B. 
Published: December 2004

Abstract2,2,′,2″,2‴‐Tetrapyridineiron(III) complex ions anchored to poly(L‐glutamate) (FeL) or poly(D‐glutamate) (FeD) were used as catalysts for the H2O2 oxidation of L(+)‐ascorbic acid at pH 7 and varying complex:polymer‐residue molar ratios [C]/[P]. Evidence is produced that the reaction is a composite process reflecting contributions from parallel pathways, one of which corresponds to a catalytic route and is [H2O2]‐independent and the other to an uncatalyzed electron‐transfer process between the ascorbate anion and hydrogen peroxide. Stereospecific effects in the catalysis are observed on increasing the complex:polymer ratio, which corresponds to an increase of the amount of α‐helical fraction in the polypeptide supports (xa). Thus, at [C]/[P] = 0.01 (xa < 0.05), kFeD/kFeL = 1.0; but at [C]/[P] = 0.20 (xa ≈ 0.70), kFeD/kFeL = 4.0 ± 0.5, kFeD and kFeL being the second‐order rate constants of the electron‐transfer reaction between the FeD or FeL isomer of the asymmetric catalyst and the L‐ascorbate anion. The activation energies were found to increase markedly on going from the former to the latter complex:polymer ratio but, at the same time, to exhibit equal values with both enantiomeric catalysts. Stereoselectivity therefore appears to be an entropy‐controlled process, arising from the conformational rigidity of the precursor complex, which very likely sees the substrate molecules bound to the chiral residues of the ordered polymer surrounding the active sites. The implications of the stereochemical features of the substrate–catalyst adduct on the mechanism of electron transfer are also discussed. Evidence is presented that the asymmetric [Fe(tetpy)(OH)2]+–polyelectrolyte systems play the additional role of environmental controller of the uncatalyzed oxidation of the L‐ascorbate anion.
Effects of pressure on the composition density distribution in the ultracentrifuge
Authors: Sharp Dan S. , Ifft James B. 
Published: December 2004

AbstractThe effects of pressure on the composition density distribution in a binary density gradient at sedimentation equilibrium in the analytical ultracentrifuge are rigorously examined. A computer algorithm is described for the necessary iterative computations. The pressure effect is found to be significant in runs where a long column length, high angular velocity, and a salt with a high pressure correction coefficient are simultaneously employed. Such conditions are sometimes encountered in current studies in which high precision is required to measure the compressibility of proteins.
Quasielastic light scattering by biopolymers. VI. Diffusion of mononucleosomes and oligonucleosomes in the presence of static and sinusoidal electric fields
Authors: Schmitz Kenneth S. 
Published: December 2004

AbstractQuasielastic light scattering and electrophoretic light scattering studies were carried out on mononucleosome and oligonucleosome systems. The electrophoretic light scattering experiments employed static and sinusoidal electric fields. Data are presented that suggest at least two relaxation modes. It is proposed that the small amplitude sinusoidal field effectively polarizes the ion atmosphere about the polyion, thus leading to an induced dipole moment that varies sinusoidally in time. This model is, in essence, an extension of the current interpretation of low‐frequency dielectric dispersion data on DNA as being due to fluctuations of counterions along the polyion.
15N‐NMR spectroscopy. 34. Stereospecificity of the polymerization of D,L‐leucine N‐carboxyanhydride and γ‐OMe‐D,L‐glutamic acid N‐carboxyanhydride
Authors: Kricheldorf H. R. , Hull William E. 
Published: December 2004

AbstractD,L‐Leucine‐N‐carboxyanhydride (D,L‐Leu‐NCA) and γ‐methyl‐D,L‐glutamic acid N‐carboxyanhydride (γ‐OMe‐D,L‐Glu‐NCA) were synthesized with ca. 2.5% 15N enrichment. Their polymerizations were conducted under a variety of conditions using benzylamine, triethylamine potassium tert‐butanolate, and pyridine as initiators. The 40.55‐MHz 15N‐nmr spectra of the resulting stereocopolypeptides measured in trifluoroacetic acid display at least four signals, representing the isotatic, syndiotactic, and two heterotactic triads. From the signal intensities it was concluded that these NCAs behave nearly identically. With benzylamine initiation the formation of isotactic blocks is slightly favored, and they are still more predominant when strong bases are used as initiators. Initiation by pyridine favors the formation of syndiotactic sequences. However, in all cases the average lengths of the stereoblocks never exceeded 4 monomer units. The low stereospecificity of most polymerizations of D,L‐NCAs is confirmed by the high degree of solubility of the resulting poly(D,L‐amino acids) in aprotic solvents. Penultimate effects are weak or absent, so that most polymerizations follow Bernoullian type statistics. Deviations from these statistics were found for polymerizations in pyridine.
Structure of methylene blue–DNA complexes studied by linear and circular dichroism spectroscopy
Authors: Nordén Bengt , Tjerneld Folke 
Published: December 2004

AbstractBradley et al. [(1972) Biopolymers 11, 645–652] used electro‐optical measurements to show that methylene blue (MB), like acridine orange, in its DNA complex is oriented more or less perpendicular to the helix axis as expected if intercalated. High‐precision flow linear dichroism (LD) here confirms that MB is coplanar with the DNA bases at low dye/DNA binding ratios and low ionic strengths. CD shows two origins of induced optical activity for the transition of lowest energy (polarized parallel to the long‐axis of the dye molecule): at low binding ratios (r < 0.05), a weak monomeric CD with the same shape as the absorption curve is observed, while at higher binding ratios, a strong exciton CD dominates due to interaction between pairs of MB ligands. The monomeric CD spectrum shows a remarkable dependence on ionic strength: it is negative in the absence of extra salt, but changes sign (at ca 20 mM NaCl or 0.15 mM MgCl2) and becomes essentially the positive mirror‐image spectrum at high ionic strengths (>300 mM Na+ or >0.4 mM Mg2+). Nondegenerate coupled‐oscillator theory can explain the CD in terms of interactions of transition moments of the dye and the nearest nucleotide bases and indicates a change between two intercalation geometries: a Lerman type of mode, denoted γ−, and an orthogonal mode, denoted γ+. This rotation of MB in the base‐pair pocket is accomplished at Na+ and Mg2+ concentrations when the phosphates are effectively screened and the result suggests a more localized bonding of Mg2+ than is expected from simple polyelectrolyte models. The exciton effect at high binding ratios, observed both in CD and in LD, can be interpreted in terms of an interaction between an intercalated and a nonintercalated MB. The geometry of this “accidental” dimer is consistent with a location of the nonintercalated MB in the minor groove, bridging the strands by the positively charged amino groups directed towards phosphate groups. The dihedral angle of the MB pairs, corresponding to a left‐handed helix, is opposite to that with acridine orange and proflavine on DNA, indicating that the latter ligands bind to DNA in a different way.
A circular dichroism microspectrophotometer
Authors: Maestre M. F. , Katz J. E. 
Published: December 2004

AbstractA microscope capable of measuring the CD of intact single eukaryotic cells, DNA microcrystals, and other microscopic structures has been constructed and tested. It can measure the CD spectra in the 200‐ and 800‐nm wavelength range and consists of a modification to a standard Cary 60 CD machine in combination with a Zeiss uv microspectrometer. Preliminary CD spectra of red blood cells and lymphocytes are presented.
Conformational properties of microtubule protein: Their relation to the self‐assembly process in vitro
Authors: Bayley Peter M. , Clark David C. , Martin Stephen R. 
Published: December 2004

AbstractNear‐ and far‐uv CD spectra of microtubule protein preparations have been examined to study the possible role of protein conformation in relation to the kinetics of the self‐assembly of these proteins into microtubules in vitro. Although tubulin can form conformations with high helical content under apolar solution conditions, this transformation is apparently not involved in self‐assembly. There is no major perturbation of tubulin near‐uv CD by reagents and solution conditions favoring assembly. Thus, in these preparations, tubulin, as dimer and as oligomer with MAPs, is effectively in the conformation in which it undergoes self‐assembly. This conclusion is consistent with a hybrid model of assembly of microtubule protein involving direct incorporation of oligomeric species as an alternative to the condensation polymerization of tubulin dimer as the exclusive assembly mechanism.
Solid‐state geometry and conformation of linear, diastereoisomeric oligoprolines
Authors: Benedetti Ettore , Bavoso Alfonso , di Blasio Benedetto , Pavone Vincenzo , Pedone Carlo , Toniolo Claudio , Bonora Gian Maria 
Published: December 2004

AbstractWe have carried out a systematic analysis of the solid‐state conformational preferences of a number of linear homo‐oligoprolines (to the tetramer) by ir absorption and x‐ray diffraction. The peptides present different chiral sequences (tacticities), various types (urethane and amide) of N‐protecting groups, and free and blocked C‐termini (which imply different capabilities of forming H‐bonds). The following conclusions can be drawn: (i) values for the geometry of the prolyl residue and the peptide bond in the cis and in the trans conformations are proposed; (ii) in general the conformational angles φ and ψ in the linear homo‐oligoprolines have values appropriate for the polyproline II structure (conformation F); (iii) the pyrrolidine ring shows various types of puckering with no apparent relation to the backbone conformation; (iv) Pro‐Pro peptide bonds generally take the trans conformation, the few cases of cis conformation being formed by Pro residues of different chirality; (v) the single H‐bond donor — OH, when present, is always bonded to H‐acceptors, which can be either the urethane or the amide or the peptide carbonyl but never the carbonyl group of the — COOH moiety.
Electron diffraction studies of poly(α‐aminoisobutyric acid)
Authors: Malcolm B. R. 
Published: December 2004

AbstractElectron diffraction photographs of poly (α‐aminoisobutyric acid) treated with dichloracetic acid are shown to be consistent with space group R3c. This is strong evidence for a hexagonal cell in which right‐ and left‐handed 310‐helices form a honeycomb structure. It appears that the dichloracetic acid molecules are located in the centers of the holes.
X‐ray diffraction study of the interaction of the amino terminal half‐molecule of histone H4 with duplex DNA
Authors: Wachtel E. J. , Sperling R. 
Published: December 2004

AbstractThe interaction of the amino terminal half‐molecule of histone H4 with duplex DNA has been studied by fiber x‐ray diffraction. Changes induced in the diffraction pattern of B‐DNA by the presence of the bound peptide have been Fourier‐analyzed and the results presented in terms of a deweighted radial projection of the electron density. We conclude that the peptide binds on the major groove side of the sugar–phosphate chain.
Serine and β‐turns
Authors: Aubry A. , Marraud M. 
Published: December 2004

AbstractSerine is one of the most frequent residues included within β‐turns in proteins. Conformational investigations have been carried out on the LL and LD model dipeptides ButCO‐Pro‐Ser‐NHMe in the solute state by ir and nmr spectroscopies and in the solid state by x‐ray diffraction. LL and LD sequences are folded in the βI‐ and βII‐types, respectively, and in both cases a weak intramolecular interaction takes place between the NH and Oγ sites of the serine residue.
Neurophysin–neuropeptide hormone complexes: Biosynthetic origin and noncovalent interactions
Authors: Chaiken Irwin M. 
Published: December 2004

AbstractRecent studies of the neurophysins and associated neuropeptide hormones have addressed both the biosynthetic pathways by which these noncovalent protein–peptide complexes are derived in neurosecretory neurons and the nature of the noncovalent interactions likely to occur during transport and storage in neurosecretory granules within the neurons. In vitro translation of hypothalamic mRNA and sequencing of cDNA obtained from this mRNA have yielded chemical evidence that each complex of hormone and major neurophysin is made through a common precursor molecule. The mature complexes obtained upon proteolytic processing of precursors exhibit interdependent hormone binding and self‐association interactions. Photoaffinity labeling and quantitative affinity chromatography have helped detect and define the binding surfaces involved. Further study of the structural nature of these surfaces is being carried out using large neurophysin fragments obtained by limited tryptic proteolysis.
Photo‐CIDNP study of interactions of serine proteinases with their protein inhibitors
Authors: Muszkat K. A. , Weinstein S. , Khait I. , Vered M. 
Published: December 2004

AbstractPhotochemically induced dynamic nuclear polarization was used to study the accessibility of surface tyrosine and tryptophan residues in proteinases, in their protein inhibitors and in the proteinase–inhibitor complexes. The accessibility probe is the triplet of 10‐(carboxyethyl) flavin formed by optical excitation. On complex formation we observe accessibility loss in the surface tyrosines and tryptophans in the proximity of the proteinase–inhibitor contact site, and in the case of bovine pancreatic trypsin inhibitor, in more distant tyrosines as well.
Conformational and dynamic considerations in the design of peptide hormone analogs
Authors: Hruby Victor J. , Mosberg Henry I. , Sawyer Tomi K. , Knittel James J. , Rockway Todd W. , Ormberg James , Darman Paul , Chan W. Y. , Hadley Mac E. 
Published: December 2004

AbstractEfforts to understand the chemical‐physical basis for peptide hormone and neurotransmitter action requires integration of conformational parameters and biological properties. Since most peptide hormones are conformationally flexible, the question arises as to which of the manifold of conformations is of biological significance. In molecular terms, it is necessary to carefully distinguish chemical‐physical features important to binding (the binding message) from those involved in transduction (the biological activity message). One approach to this involves the design, synthesis, and conformational analysis of semirigid hormone analogs. The distinction between binding and transduction can best be examined by evaluation of full biological profiles of partial agonists, antagonists, and analogs with prolonged biological activity. Using this multidisciplinary approach, we have prepared several semirigid [Pen1]‐oxytocin antagonist analogs and evaluated their conformational properties and biological activities. Specific conformational features can be related to inhibitory activities in several cases. On the basis of structure–activity relationships and conformational considerations, we have designed a series of conformationally restricted cyclic and acyclic analogs of the linear peptide α‐melanotropin. Some of these peptides have exceptionally prolonged in vivo activity (weeks), and others exhibit superagonist potency (10,000 times the native hormone). We have evidence that potency and prolonged activity have different structural and conformational requirements. It is suggested that potency is primarily a function of receptor recognition (the binding message), whereas prolonged activity is related to transduction (the biological activity message).