bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specificity of trypsin digestion and conformational flexibility at different sites of unfolded lysozyme
Authors: Noda Yasuo , Fujiwara Keiro , Yamamoto Koji , Fukuno Takuji , Segawa Shin‐Ichi 
Published: December 2004

AbstractFourteen tryptic peptides and nine intermediates were identified as products of trypsin digestion of reduced and S‐3‐(trimethylated amino) propylated lysozyme. Kinetics of the appearance and disappearance of these products were observed by monitoring the peak areas on the chromatogram. In spite of the complicated reaction pathways, kinetics of the digestion of proteins and several intermediate products show simple decay curves with a single rate constant. In this paper, the trypsin susceptibility of the individual cleavage site is defined as a hydrolytic rate constant of the susceptible peptide bond in the presence of 10 nM trypsin. The cleavage sites of unfolded lysozyme are classified into two groups in terms of the trypsin susceptibility: one has a high susceptibility (10–20 h−1) and the other a low susceptibility (1.0–2.0 h−1). In the unfolded state of lysozyme, in conclusion, the region from residues 15 to 61 has a strong resistance to trypsin digestion; on the other hand, the C‐terminal half of the polypeptide chain is flexible enough to fit into the active site of trypsin.In addition, six kinds of pentapeptides were synthesized as analogues of lysozyme fragments including Arg 14, Arg 21, Lys 33, Arg 45, Arg 61, and Arg 73. Kinetics of typtic digestion of them were observed. Both kcat and KM were determined for these synthetic pentapeptides. The susceptibility of each cleavage site in pentapeptides is determined and compared with that corresponding in proteins. The susceptibility is usually higher when the susceptible peptide chain is flexible. However, susceptibilities of a few sites in proteins are lower than those in pentapeptides. This means that the peptapeptides, this means that the peptide chains tend to fold locally to prevent trypsin from binding to the sites. It was found that the sites of Arg 21 and Arg 45 are indeed resistant to trypsin, but the site of Lys 33 is not so much, although the hydrolytic rate at Lys 33 itself is extremely slow. © 1994 John Wiley & Sons, Inc.
Electrophoretic mobility of DNA in gels. II. Systematic experimental study in agarose gels
Authors: Heller C. , Duke T. , Viovy J. L. 
Published: December 2004

AbstractA systematic study has been undertaken to prove or disprove the predictions of a revised reptation model, biased reptation with fluctuations (BRF). Our data, which scan about two orders of magnitude of DNA sizes and of electric fields, and a fourfold range of gel concentrations, are in qualitative and quantitative agreement with the model and support the applicability of this theory to DNA gel electrophoresis. In particular, we show that the mobility in the compression zone scales as the first power of the electric field, and that the limit of separation scales as the inverse first power of the electric field, for low enough fields. © 1994 John Wiley & Sons, Inc.
Thermodynamic strategies for stabilizing intermediate states of proteins
Authors: Haynie Donald T. , Freire Ernesto 
Published: December 2004

AbstractThis paper presents three theorems pertaining to thermodynamic properties of the intermediate (e.g., molten globule) state of proteins exhibiting such a conformation in the presence of GuHCl or urea. The theorems are proved for the three‐state case using the denaturant binding model and the linear extrapolation model; their utility is illustrated via applications to examples in the literature. Theorem One states that the denaturant activity that maximizes the population of a partly folded conformation is at any temperature independent of the Gibbs free energy difference between the intermediate and native states. This result holds for both models of protein–denaturant interaction. The second theorem claims that the population maximum is independent, of the denaturant association constant for the denaturant binding model. Theorem Three, which also applies to both models considered here, states that at the temperatures corresponding to the extrema in the population of the intermediate, the enthalpy change of the intermediate is equal to the excess enthalpy function, an experimentally accessible quantity. In the absence of denaturant, the enthalpy change of the intermediate state at the population extrema can be written as a function of the thermodynamic parameters of the unfolded state alone. These results, which can be applied to systems of any number of states under certain conditions, should aid in the optimization of conditions employed for experimental studies of partly organized states of proteins. © 1994 John Wiley & Sons, Inc.
Measuring the geometry of DNA grooves
Authors: Stofer E. , Lavery R. 
Published: December 2004

AbstractWe present a new method for measuring the widths and depths of the grooves formed within DNA helices. This method overcomes the limitations of simply measuring interstrand phosphate–phosphate distances and has the advantage of yielding continuous values for groove geometry along a DNA fragment. In the case of oligonucleotides, it also clearly indicates the zones in which grooves exist, bounded by two phosphodiester backbones. The methodology has been developed within the Curves algorithm for studying irregular DNA geometries and is based on the optimal, and generally curved, helical axis obtained by this analysis. © 1994 John Wiley & Sons, Inc.
Folding polypeptide α‐carbon backbones by distance geometry methods
Authors: Aszóadi A. , Taylor W. R. 
Published: December 2004

AbstractPolypeptide α‐carbon backbones were modeled as freely rotating chains made up of spherical monomers. The monomers were assigned an abstract binary “hydrophobicity” property that could be either present or absent. Under the assumption that “hydrophobic” residues tend to cluster together, away from the polar solvent, three‐dimensional conformations of random copolymers of “hydrophobic” and “hydrophilic” monomers were calculated by a novel algorithm based on distance geometry techniques. The simulated molecules were globular and compact, in shape, and possessed distinct hydrophobic cores, indicating that our method was capable of reproducing some of the important global features of real polypeptides. © 1994 John Wiley & Sons, Inc.
On higher buckling transitions in supercoiled DNA
Authors: Schlick Tamar , Olson Wilma K. , Westcott Timothy , Greenberg Jerry P. 
Published: December 2004

AbstractA combination of detailed energy minimization and molecular dynamics studies of closed circular DNA offers here new information that may be relevant to the dynamics of short DNA chains and/or low superhelical densities. We find a complex dependence of supercoiled DNA energies and geometries on the linking number difference ΔLk as physiological superhelieal densities (|σ| ∼ 0.06) are approached. The energy minimization results confirm and extend predictions of classical elasticity theory for the equilibria of elastic rods. The molecular dynamics results suggest how these findings may affect the dynamics of super‐coiled DNA.The minimization reveals sudden higher order configurational transitions in addition to the well‐known catastrophic buckling from the circle to the figure‐8. The competition among the bending, twisting, and self‐contact forces leads to different families of supercoiled forms. Some of those families begin with configurations of near‐zero twist. This offers the intriguing possibility that nicked DNA may relax to low‐twist forms other than the circle, as generally assumed. Furthermore, for certain values of ΔL𝓀, more than one interwound DNA minimum exists. The writhing number as a function of ΔL𝓀 is discontinuous in some ranges; it exhibits pronounced jumps as ΔL𝓀 is increased from zero, and it appears to level a characteristic slope only at higher values of ΔL𝓀. These findings suggest that supercoiled DNA may undergo systematic rapid interconversions between different minima e both close in energy and geometry.Our molecular dynamics simulations reveal such transitional behavior. We observe the macroscopic bending and twisting fluctuations of interwound forms about the global helix axis as well as the end‐over‐end tumbling of the DNA as a rigid body. The overall mobility related to |σ| and to the bending, twisting, and van der Waals energy fluctuations. The general character of molecular motions is thus determined by the types of energy minima found at a given ΔL𝓀. Different time scales may be attributed to each type of motion: The overall chain folding occurs on a time scale almost an order of magnitude faster than the end‐over‐end tumbling. The local bending and twisting of individual chain residues occur at an even faster rate, which in turn correspond to several cycles of local variations for each large‐scale bending and straightening motion of the DNA. © 1994 John Wiley & Sons, Inc.
Relaxed‐residue conformational mapping of the three linkage bonds of isomaltose and gentiobiose with MM3(92)
Authors: Dowd Michael K. , Reilly Peter J. , French Alfred D. 
Published: December 2004

AbstractIsoenergy surfaces were calculated for the α‐ and β‐anomers of isomaltose and gentiobiose, based on 46,656 conformers for each disaccharide. Low‐energy regions exist for each of the three staggered positions about the C‐5′  C‐6′ bonds, and known crystal structures lie in two of these regions. As expected, the molecular partition function showed greater flexibility for these three‐bond‐linked disaccharides than for comparable two‐bond‐linked structures. A model miniature crystal of gentiobiose accounts for most of the remaining structural differences between the modeled isolated molecule and the crystal structure. Based on models of isolated molecules of isomaltose and gentiobiose, the predicted Boltzmann‐weighted nmr coupling constants were satisfactory, as were predicted optical rotations for gentiobiose. © 1994 John Wiley & Sons, Inc.
Conformation of the flexible bent helix of Leu1‐zervamicin in crystal C and a possible gating action for ion passage
Authors: Karle Isabella L. , Flippen‐Anderson Judith L. , Agarwalla S. , Balaram P. 
Published: December 2004

AbstractThe membrane channel‐forming polypeptide, Leu1‐zervamicin, Ac‐Leu‐Ile‐Gln‐Iva‐Ile5‐Thr‐Aib‐Leu‐Aib‐Hyp10‐Gln‐Aib‐Hyp‐Aib‐Pro15‐Phol (Aib: α‐aminoisobutyric acid; Iva: isovaline; Hyp: 4‐hydroxyproline; Phol: phenylalininol) has been analyzed by x‐ray diffraction in a third crystal form. Although the bent helix is quite similar to the conformations found in crystals A and B, the amount of bending is more severe with a bending angle ≈ 47°. The water channel formed by the convex polar faces of neighboring helices is larger at the mouth than in crystals A and B, and the water sites have become disordered. The channel is interrupted in the middle by a hydrogen bond between the OH of Hyp (10) and the NH2 of the Gln (11) of a neighboring molecule. The side chain of Gln (11) is wrapped around the helix backbone in an unusual fashion in order that it can augment the polar side of the helix. In the present crystal C there appears to be an additional conformation for the Gln (11) side chain (with ≈ 20% occupancy) that opens the channel for possible ion passage. Structure parameters for C85H140N18O22 · xH2O · C2H5OH are space group P212121, a = 10.337(2) Å, b = 28.387(7) Å, c = 39.864(11) Å, Z = 4, agreement factor R = 12.99% for 3250 data observed > 3σ(F), resolution = 1.2 Å. © 1994 John Wiley & Sons, Inc.
Conformation and molecular dynamics calculations on uteroglobin fragment 18‐47
Authors: Improta Sabina , Pastore Annalisa , Mammi Stefano , Peggion Evaristo 
Published: December 2004

AbstractThe conformational properties of fragment 18–47 of rabbit uteroglobin in aqueous solution containing SDS micelles were investigated by two‐dimensional nmr spectroscopy and molecular dynamics calculations. The fragment comprises helices II and III and the β‐turn connecting the two helices.The nmr results and nmr‐restrained molecular dynamics calculations showed that in the isolated fragment the elements of secondary structure present in the intact protein are preserved only in part. Specifically, a well‐defined α‐helix was found in the sequence 33–44, corresponding to helix III of uteroglobin, while the regions of helix II and β‐turn are characterized by high flexibility in the fragment. © 1994 John Wiley & Sons, Inc.
Quadratic nonlinear optical susceptibility of helical polymers
Authors: Lalov I. J. , Atanasov R. D. 
Published: December 2004

AbstractThe quadratic nonlinear optical susceptibility of a solution of helical polymers and of samples with helices oriented parallel to each other is calculated for regions of characteristic vibrations and of their overtones. The important role of electrooptical and of mechanical anharmonicity for exhibition of overtones in nonlinear spectroscopy is shown. The possibility of the appearance of the giant polarizabilities near bound overtone states is analyzed. The overtone spectrum of amide I is modeled numerically. © 1994 John Wiley & Sons, Inc.
Shape complementarity at protein–protein interfaces
Authors: Norel Raquel , Lin Shuo L. , Wolfson Haim J. , Nussinov Ruth 
Published: December 2004

AbstractA matching algorithm using surface complementarity between receptor and ligand protein molecules is outlined. The molecular surfaces are represented by “critical points,” describing holes and knobs. Holes (maxima of a shape function) are matched with knobs (minima). This simple and appealing surface representation has been previously described by Connolly [(1986) Biopolymers, Vol. 25, pp. 1229–1247]. However, attempts to implement this description in a docking scheme have been unsuccessful (e.g., Connolly, ibid.). In order to decrease the combinatorial complexity, and to make the execution time affordable, four critical hole/knob point matches were sought. This approach failed since some bound interfaces are relatively flat and do not possess four critical point matches. On the other hand, matchings of fewer critical points require a very time‐consuming, full conformational (grid) space search [Wang, (1991) Journal of Computational Chemistry, Vol. 12, pp. 746–750]. Here we show that despite the initial failure of this approach, with a simple and straightforward modification in the matching algorithm, this surface representation works well. Out of the 16 protein‐protein complexes we have tried, 15 were successfully docked, including two immunoglobulins. The entire molecular surfaces were considered, with absolutely no additional information regarding the binding sites. The whole process is completely automated, with no manual intervention, either in the input atomic coordinate data, or in the matching. We have been able to reach this level of performance with the hole/knob surface description by using pairs of critical points along with their surface normals in the calculation of the transformation matrix. The success of this approach suggests that future docking methods should use geometric docking as the first screening filter. As a geometrically based docking methodology predicts correct, along with incorrect, receptor‐ligand bound conformations, all solutions need to undergo energy screening to differentiate between them. © 1994 John Wiley & Sons, Inc.
Solution three‐dimensional structure of surfactin: A cyclic lipopeptide studied by1H‐nmr, distance geometry, and molecular dynamics
Authors: Bonmatin Jean‐Marc , Genest Monique , Labbé Henri , Ptak Marius 
Published: December 2004

AbstractThe solution three‐dimensional structure of the protonated [Leu7]‐surfactin, an hepta‐peptide extracted fromBacillus subtilis, has been determined from two‐dimensional1Hnmr performed in2H6‐dimethylsulfoxide and combined with molecular modeling. Experimental data included 9 coupling constants, 61 nuclear Overhauser effect derived distances, NH temperature coefficients, and13C relaxation times. Two distance geometry (DISMAN) protocols converged toward models of the structure and the best of them were refined by restrained and unrestrained molecular dynamics (GROMOS). Two structures in accord with the set of experimental constraints are presented. Both are characterized by a “horse saddle” topology for ring atoms on which are attached the two polar Glu and Asp side chains showing an orientation clearly opposite to that of the C11–13aliphatic chain. Amphipathic and surface properties of surfactin are certainly related to the existence of such minor polar and a major hydrophobic domains. The particular “claw” configuration of acidic residues observed in surfactin gives important clues for the understanding of its cation binding and transporting ability. © 1994 John Wiley & Sons, Inc.
Thermodynamic basis of site‐specific cooperativity
Authors: Cera Enrico Di 
Published: December 2004

AbstractCooperative phenomena in biological macromolecules arise from the interaction of many distinct subsystems, such as structural domains or binding sites. Cooperative properties of the system as a whole, like protein folding or allosteric transitions, are subject to the restrictions imposed by thermodynamic stability. These restrictions, however, do not apply in the case of individual subsystems open to interactions with the rest of the macromolecule. The site‐specific properties of such subsystems can be understood in general thermodynamic terms from those of a multicomponent system under particular conditions. The analogy provides a thermodynamic basis for site‐specific Cooperativity. © 1994 John Wiley & Sons, Inc.
Molecular dynamics studies of the human CD4 protein
Authors: Ptaszek L. M. , Vijayakumar S. , Ravishanker G. , Beveridge D. L. 
Published: December 2004

AbstractA dynamical model for an N‐terminal fragment of the human CD4 protein has been determined by computer simulation. The protein has been studied both in vacuo and in solution. Data from both simulations agree moderately well with each other and with the crystal structure. All elements of secondary structure were retained during simulation. Point mutation and sequence replacement studies have shown that a loop in CD4, residues 40–52, is involved in binding with gp120, the human immunodeficiency virus surface glycoprotein.1,2 Our results show that the gp120‐binding loop and a few regions which bind to monoclonal antibodies and class II MHC molecules are the most highly motile areas of the protein. These results are consistent with the suggestion that CD4 binds to target molecules by using induced‐fit contacts. © 1994 John Wiley & Sons, Inc.
13C‐labeled oligodeoxyribonucleotides: A solution study of a CCAAT‐containing sequence at the nuclear factor I recognition site of human adenovirus
Authors: Wu Jian , Serianni Anthony S. 
Published: December 2004

AbstractThe solution behavior of the single‐stranded CCAAT‐containing octamer 1, d(AGCCAATA), that comprises part of the nuclear factor I (NF‐I) recognition site at the origin of replication of human adenovirus has been studied by nmr spectroscopy at 500 and 600 MHz. Proton resonance assignments for 1 were aided by selective 13C enrichment at C1′ of A1 or A5. High‐resolution 13C‐1H heteronuclear multiple‐bond coherence spectra of the 13C‐labeled oligomers permitted the selective detection of furanosyl ring protons within each labeled residue due to short‐ and long‐range 13C‐1H couplings to the enriched C1′. The resulting assignments provided firm starting points in the interpretation of double quantum filtered correlated spectra, yielding information supplemented by total correlated spectroscopy (TOCSY) and rotating frame nuclear Overhauser effect spectroscopic data to completely assign the 1H‐nmr spectrum of 1 and extract 3JHH values for furanose con‐formational analysis. Several 13C‐1H spin‐coupling constants within the 13C‐enriched A1 or A5 residues were measured from cross‐peak shifts in TOCSY spectra, and their signs determined by inspection of the relative orientations of these shifts. 1H‐2‐H and 13C‐1H spin‐couplings both indicate a preference (> 75%) for south (C2′‐endo) conformations by the furanosyl rings of 1. © 1994 John Wiley & Sons, Inc.
Theoretical conformational analysis of the opioid δ antagonist H‐Tyr‐Tic‐Phe‐OH and the μ agonist H‐Tyr‐D‐Tic‐Phe‐NH2
Authors: Wilkes Brian C. , Schiller Peter W. 
Published: December 2004

AbstractA molecular mechanics study (grid search and energy minimization) of the highly δ receptor‐selective δ opioid antagonist H‐Tyr‐Tic‐Phe‐OH (TIP; Tic: tetrahydroisoquinoline‐3‐car‐boxylic acid) resulted in four low energy conformers with energies within 2 kcal/mol of that of the lowest energy structure. These four conformers contain trans peptide bonds only and represent compact structures showing various patterns of aromatic ring stacking. The centrally located Tic residue imposes several conformational constraints on the N‐terminal dipeptide segment; however, the results of molecular dynamics simulations indicated that this tripeptide still shows some structural flexibility, particularly at the Phe3 residue. Analogous studies performed with the structurally related μ receptor‐selective μ agonist H‐Tyr‐D‐Tic‐Phe‐NH2 resulted in low energy structures that were also compact but showed patterns of ring stacking different from those obtained with TIP. Superim‐position of low energy conformers of TIP and H‐Tyr‐D‐Tic‐Phe‐NH2 revealed that the Phe3 residues of the L‐Tic‐ and the D‐Tic peptide were always located on opposite sides of the plane defined by the Tic residue, thus providing an explanation for the distinct activity profiles of the two compounds in structural terms. Attempts to demonstrate spatial overlap between the pharmacophoric moieties of low energy conformers of TIP and the nonpeptide δ antagonist naltrindole were made by superimposing either the Tyr1 and Tic2 aromatic rings and the N‐terminal amino group or the Tyr1 and Phe3 aromatic rings and the N‐terminal amino group of the peptide with the corresponding aromatic rings and nitrogen atom in the alkaloid structure. In each case a low energy structure of TIP was found that showed good spatial overlap of all three specified pharmacophoric groups. These two conformers may represent candidate structures for the δ receptor‐bound conformation of TIP. © 1994 John Wiley & Sons, Inc.
α,β‐Dehydro‐amino acid residues in the design of peptide structures: Synthesis, crystal structure, and molecular conformation of two homologous peptides—N‐Ac‐Dehydro‐Phe‐L‐Leu‐OCH3and N‐Ac‐Dehydro‐Phe‐NorVal‐OCH3
Authors: Sharma Pushkar , Narula Punit , Singh Tej P. 
Published: December 2004

AbstractThe dehydro‐residue containing peptides N‐Ac‐dehydro‐Phe‐L‐Leu‐OCH3(I) and N‐Ac‐dehydro‐Phe‐NorVal‐OCH3(II) were synthesized by the usual workup procedures. The peptides crystallize from their solutions in methanol in space group P65: (I)a=b= 12.528(2) Å,c= 21.653(5) Å; (II)a=b= 12.532(2) Å,c= 21.695(4) Å. The structures were determined by direct methods. Both peptides adopt similar conformations with ϕ,ψ of dehydro‐Phe as follows: (I) −57.0(5)° and −37.0(5)°; (II) −56.0(5),° and −37.5(5)°. The observed data on dehydro‐Phe when placed at the (i+ 1) position show that the ϕ,ψ values of dehydro‐Phe are either −60°, 140° or −60°, −30°. The conformation of −60°, 140° can be accommodated only with a flexible residue at the (i+ 2) position while the ϕ,ψ values of −60°, −30° are obtained with a bulky residue at the (i+ 2) position as in the present structures. The molecules are packed in a helical way along thecaxis. These are held by two strong intermolecular hydrogen bonds involving both NH as donors and acetyl group and dehydro‐Phe oxygen atoms as acceptors. © 1994 John Wiley & Sons, Inc.