bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new approach to the problem of docking two molecules: The ellipsoid algorithm
Authors: Billeter M. , Havel T. F. , Kuntz I. D. 
Published: December 2004

AbstractA recently developed method of constrained optimization, known as the ellipsoid algorithm, is explored as a tool for determining sterically acceptable interactions between two molecules. These interactions are described by constraints on intermolecular distances. Upper distance bounds between specific pairs of atoms, one in the ligand and one in the enzyme, were used in two different types of docking problems. In the first type, knowledge of a small set of well‐defined upper distance constraints was assumed, e.g., specific information about hydrogen bonds or experimentally determined atom–atom distances. The second approach assumes only knowledge of the location of the binding site of one of the molecules, but nothing about how the second, typically small, molecule is packed into this site. In this case, a set of upper distance bounds was used one at a time to explore systematically all possible ways of packing the ligand into the site. In all applications, van der Waals repulsions were used to define a lower distance bound for each atom pair. To specify the relative orientation of the two molecules, a new set of variables had to be introduced. They enable us to represent the set of all possible rotations in a vector space as required by the ellipsoid algorithm. Consequently, in contrast to the usual Euler angles, they assure additivity, so that the result of multiple changes of the variables is not sensitive to the order in which they are performed. In addition to the six degrees of freedom involved in docking rigid objects, conformational flexibility can be explicitly included in the individual molecules. Applications discussed include the docking of two macromolecules and the formation of an enzyme–inhibitor complex. For each constraint set tested, ten randomly chosen starting structures were optimized. The time for each of the runs was between 3 min and 1.3 h on a VAX 750 or a Microvax II; in larger problems, the time is spent primarily in van der Waals checking. The advantages of the ellipsoid algorithm compared to other methods are its robustness with respect to local minima, and the relatively small amounts of computer time and memory that it needs. A final discussion compares this method to some other docking methods, including distance geometry and the matching of molecular surfaces.
Nmr studies on the presence of domain structures in polysaccharides
Authors: Lacelle Serge , Gerstein Bernard C. 
Published: December 2004

AbstractA variety of nmr transient techniques demonstrate the absence of domain structures in powders of α‐ and β‐cyclodextrins, dextran B512F, and their “deuterated” analogs where deuterium replaces exchangeable protons. Cyclodextrins and dextran are inferred to be homogeneously ordered and disordered one‐phase systems, respectively. We show how erroneous results concerning the presence and sizes of rigid and mobile domains can be reached from the interpretations of two‐component free induction decays and spin–lattice relaxation behavior of polysaccharides. In our approach, we have measured 1H free induction decays and lineshapes, and 1H spin–lattice and dipolar relaxation times, in addition to using Goldman–Shen experiments and 13C cross‐polarization magic‐angel sample spinning. Self‐consistent nmr results are suggested as essential means to corroborate conclusions concerning domain structures in biopolymers.
β‐Turns in serine‐containing linear and cyclic models
Authors: Hollósi M. , Kövér K. E. , Holly S. , Fasman G. D. 
Published: December 2004

AbstractTetrapeptides, Cbz‐Gly‐X‐Y‐Gly‐OSt (1–4)—as well as cyclic systems, cyclo[NH‐(CH2)n‐CO‐Gly‐Ser(OX)‐Ser(OX)‐Gly] (5 and 6; n = 4 and 2, X = But or H), have been synthesized in order to compare the CD spectrum of linear and cyclic β‐turn models containing either a protected or a free hydroxyl of the serine residue. In extremely dilute cyclohexane solution the linear models Cbz‐Gly‐Ser‐Y‐Gly‐OSt (1–3a) show class B spectra with very strong positive bands, contrary to other members of the series. Based on 200‐MHz 1H nuclear overhauser enhancement and Fourier transform ir studies, Cbz‐Gly‐Ser‐Ser(OBut)‐Gly‐OSt (3a) in dilute chloroform solution assumes a distorted type II β‐turn conformation fixed by an extended system of intramolecular H bonds. As evidenced by 1H‐nmr and FT‐IR experiments, the cyclic model cyclo[NH‐(CH2)4‐CO‐Gly‐Ser(OBut)‐ Ser(OBut)‐Gly] (5a) in a 1 : 1 mixture of (CD3)2SO‐CDCl3 is also characterized by a type II β‐turn encompassing the Ser3(OBut)‐Gly4 sequence. In water, a class B pattern was measured for this model, in good agreement with theoretical and experimental studies that show that type II β‐turns are generally characterized by class B spectra. In the protected and free OH cyclic models, cyclo[NH‐(CH2)2‐CO‐Gly‐Ser(OX)‐Ser(OX)‐Gly] (5b and 6b, X = But or H) distortions of the peptide backbone due to the loss of two CH2 groups result in the appearance of CD spectra characterized by a strong negative band near 200 nm, interpreted as a sign of the lack of β‐turn structures in these models. This observation, together with other CD data discussed in this paper, clearly show that the CD of serine‐containing β‐turn sequences strongly depends on long‐range backbone and local side‐chain interactions.
Thermodynamic models for water–protein sorption hysteresis
Authors: Bryan William P. 
Published: December 2004

AbstractSorption isotherms of water by proteins show hysteresis that appears to be due to interactions at the molecular level. Four thermodynamically consistent models for this irreversible process are presented. Hysteresis could be the result of slow, incomplete conformational changes occurring upon addition and removal of water. Conformational hysteresis would occur if a number of different conformations, each corresponding to a local free energy minimum, could be present at each pressure of water vapor. Hysteresis might result from an incomplete process of intermolecular phase annealing. Finally, hysteresis might be due to incomplete phase change if two different protein phases are present. Experimental tests for these models are presented. Further study should lead to more insight into the effects of the presence of water on protein conformation and dynamics.
Anion effects on equilibria and kinetics of the disorder–order transition of κ‐carrageenan
Authors: Austen Kevan R. J. , Goodall David M. , Norton Ian T. 
Published: December 2004

AbstractThe effect of a number of tetramethylammonium salts on the equilibria and kinetics of the disorder to order transition in the polysaccharide κ‐carrageenan have been investigated. Data from the temperature dependence of optical rotation show that anion stabilization of the ordered form follows the lyotropic series I− > Br− > NO > Cl− > F−. Stopped‐flow polarimetry was used to study the kinetics of conformational ordering following a rapid increase in salt concentration. The transition to the new equilibrium position was shown to be biphasic for all of the tetramethylammonium salts studied. The rate equation for the fast phase and the temperature dependence of the observed forward rate constant accord with a cooperative dimerization process. Activation parameters for helix nucleation, ΔH* and ΔS*, vary with both salt concentration and (at constant ionic strength) the anion type, increasing through the lyotropic series from I− to F−. The slow phase shows second‐order kinetics, and is interpreted as further stabilization of the ordered form either through limited aggregation or annealing. The rate constant for the slow phase also follows the lyotropic series. Thus we have shown that both the growth and nucleation processes are anion dependent.
Electron microscopy of beaded agarose gels
Authors: Attwood T. K. , Nelmes B. J. , Sellen D. B. 
Published: December 2004

AbstractElectron microscopy has been carried out on sections of beaded agarose with a wide range of thicknesses, and the results have been analyzed by means of stereological theory using computer graphics. The results agree with a randomly orientated system in which, for 4% gels, the mean molecular weight per unit length of the fiber system is 110 kg mol−1 nm−1, and the number average interjunction length is 37 nm, with an asymmetrical distribution resembling a Maxwell‐Boltzmann distribution. The spatial distribution of the structure is not uniformly random and there seem to be mi microvoids.
Induced CD provides evidence for helical solution conformation in cellulosic chains
Authors: Ritcey Anna M. , Gray Derek G. 
Published: December 2004

AbstractEvidence for a helical contribution to the conformation of methylcellulose in dilute solution is given by CD measurements. Congo red binds to methylcellulose in dilute aqueous solution and becomes optically active. The shape of the induced CD spectra is as predicted by exciton coupling for a helical arrangement of chromophores. The magnitude of the induced CD changes reversibly with temperature, decreasing upon heating. The dimer analogue of the polymer, prepared by acid methanolysis, does not show this effect. These observations suggest that the induced optical activity reflects the conformational dissymmetry of the polymer. Analogous experiments with the cellulose oligomers (cellotriose through cellohexaose) show that five anhydroglucose units are necessary before asymmetry is induced upon dye binding.
Base sequence effects in double‐helical DNA. II. Configurational statistics of rodlike chains
Authors: Maroun Rachid C. , Olson Wilma K. 
Published: December 2004

AbstractMatrix generator techniques have been adapted to account for precise structural features of the nucleotide repeating unit and to translate the primary sequence of DNA base pairs into three‐dimensional structures. Chains have been constructed to reflect the local sequence‐dependent differences of bending and twisting of adjacent residues and various overall chain properties, including the average unperturbed moments of the end‐to‐end vector r and the mean angular orientation (〈γ〉 between base pair normals, 〈ϕ1〉 between long axes, and 〈ϕ2〉 between short axes) of terminal chain residues, have been computed. The chain backbone is treated implicitly in terms of the spatial fluctuations of successive base pairs. Motions are limited to low‐energy perturbations of the standard B‐DNA helix. Approximate potential energy schemes are used to represent the rules governing the patterns of local base–base morphology and flexibility. Theoretical predictions are compared with experimental observations at both the local and the macro‐molecular level. Initial applications are limited to the rodlike poly(dA) · poly(dT) and poly(dG) · poly(dC) helices. The former duplex is found to be more compressed and the latter more extended than random‐sequence DNA of the same chain length. The flexibility of the duplexes as a whole is described in terms of the average higher moments of the displacement vector ρ = r ‐ 〈r〉 and the likelihood of chain cyclization is estimated from the three‐dimensional Hermite series expansions of the displacement tensors. Emphasis is placed on theoretical methodology and the practical relevance of the calculated chain moments to observed physical properties.
Collapse of a polypeptide chain as a result of the intramolecular formation of antiparallel β‐sheets
Authors: Tilstra Luanne F. , Mattice Wayne L. 
Published: December 2004

AbstractThe folded nature of an intramolecular antiparallel β‐sheet suggests that the introduction of this structure into a statistical coil might be accompanied by a contraction of the chain. The magnitude of the contraction, and the conditions that produce the maximum contraction, have been assessed by the combination of generator matrices with an earlier formulation for the configuration partition function. The results show that the mean square dimensions do indeed pass through a minimum upon the transition from a statistical coil to an antiparallel β‐sheet. The depth of the minimum is relatively insensitive to the values of δ and τ, provided the assignments are within the physically sensible range. (The borders of the ordered region are assumed to be of higher energy than the interior.) In contrast with the depth of the minimum, the β‐sheet content that produces the minimum is quite sensitive to plausible variation in δ and τ. A much greater collapse of the chain can be produced by antiparallel β‐sheet formation than that found in the course of the helix–coil transition. The collapse may cause the volume pervaded by the chain to come within an order of magnitude of the volume characteristic of the globular state.
Conformational studies of N‐acetyl‐N′‐methylamide derivatives of α‐aminobutyric acid, norvaline, and valine. II. Conformational energy calculations and comparison with experimental results
Authors: Abe Akihiro , Yamazaki Toshimasa 
Published: December 2004

AbstractConformational analyses on a series of dipeptides CH3—C*O—NH—CH(R)—C*O—HN—CH3 with side chains such as R = CH2CH3, CH2CH2CH3, and CH(CH3)2 are described. Calculations were carried out by using semiempirical potential energy functions of Brant et al. The results were compared with those reported by Vásquez et al. and Chuman et al., who employed the ECEPP program in their analyses. The averages of the vicinal coupling constant J and the side‐chain conformer fractions p(χ1) and p(χ2)′ were estimated therefrom for preferred conformations. The characteristic features of the experimental observations derived from the 1H‐nmr measurements are reasonably well reproduced by these calculations.
Stacking and edge‐to‐edge associations of antitumoral ellipticine derivatives are controlled in solution by interactions involving their nitrogen sites
Authors: Sizun P. , Auclair C. , Lescot E. , Paoletti C. , Perly B. , Fermandjian S. 
Published: December 2004

Abstract1H chemical shift dilution experiments on the cytotoxic drugs 2‐methylellipticinium 1 and its methylated still active analogues 2,6‐dimethylellipticinium 2 and 1,2‐dimethylellipticinium 3 indicate that the three chromophores autoassociate in dimers, trimers, and larger aggregates. The results suggest that the same chromophores are both stacked via transannular π interactions and associated edge to edge via interactions involving the nitrogen atoms such that layer structures similar to those observed in crystals could be formed at high concentration. Substitution with a methyl group on the N6 position or the C1 position near the N, results in analogues displaying an association constant significantly reduced when compared to parent compound 1. This decrease is attributed to the loss or strength weakening of the forces involving nitrogen atoms rather than to the steric influence of the methyl substituents on the stacking of chromophores. The results are further discussed in terms of the various modes of binding of the ellipticines to DNA.
The ligation and flexibility of four‐arm DNA junctions
Authors: Petrillo Mary L. , Newton Colin J. , Cunningham Richard P. , Ma Rong‐Ine , Kallenbach Neville R. , Seeman Nadrian C. 
Published: December 2004

AbstractFour‐arm DNA branched junctions are stable analogs of Holliday recombination intermediates, constructed from oligonucleotides. The conformational flexibility of junctions can be estimated by ligating them together and determining the set of closed macrocyclic products that are obtained among the linked units. We have performed a series of these experiments, using pairs of sticky ends that flank each of the six angles of a four‐arm junction. In every case, the ligated junctions are separated by 20 nucleotide pairs, about two turns of DNA. All expected short linear products, starting with dimers, are observed for all ligations. All ligations result in a macrocyclic series that begins with trimers. Thus, over the time scale of these reactions, the arms of this junction can form angles as low as 60°. The response of this junction to torsional stress has been tested in a companion experiment. A smaller version of this same four‐arm junction has been oligomerized so that successive junctions are separated by 16 nucleotide pairs, approximately 1.5 turns of DNA. If junctions were as rigid as linear duplex DNA, this system would not be expected to form macrocycles until the continuous chain approaches the Shore–Baldwin limit, ca. 160 base pairs. However, macrocyclic closure is observed in a regular ligation ladder, starting from tetramers. Model building suggests that the most likely explanation for the observed closure is that the junction adopts two different conformations, which bend the continuous strand toward opposite grooves. The junction structures formed by these ligations represent fluctuations from equilibrium structures.
Models for the solution state structure of the (6–4) photoproduct of thymidylyl‐(3′ → 5′)‐thymidine derived via a distance‐ and angle‐constrained conformation search procedure
Authors: Taylor John‐Stephen , Garrett Daniel S. , Wang Michael J. 
Published: December 2004

AbstractThe further spectroscopic analysis and molecular modeling of the recently reported (6–4) photoproduct of thymidylyl‐(3′ → 5′)‐thymidine is described. Three‐hundred megahertz equilibrium difference nuclear Overhauser effect (NOE) spectra were obtained for the four proton singlets of the molecule, two of which have uncovered previously unreported NOEs between the TpH3′ proton and the TpH6 and pT methyl protons. Torsion angle and interproton distance information was derived from coupling constants, difference NOE data, and molecular mechanics calculations. This information, along with softened van der Waals calculations and ring‐closure constraints, was used to constrain conformation searches utilizing the SYBYL molecular modeling program subroutine SEARCH. Sets of angles derived from the ring‐search procedure were then used to construct three structures whose geometries were optimized by the energy minimization subroutines MAXIMIN and SIMPLEX. One‐, two‐, and three‐state models composed of these three structures are proposed for the solution state structure of the (6–4) product. These models are energetically sound and are consistent with the nmr data. The three derived structures are also compared to B‐form TpT.
Solid‐state conformations of aminosuccinyl peptides: Crystal structure of tert‐butyloxycarbonyl‐L‐leucyl‐L‐aminosuccinyl‐L‐phenylalaninamide
Authors: Capasso S. , Mazzarella L. , Sica F. , Zagari A. 
Published: December 2004

AbstractThe protected tripeptide tert‐butyloxycarbonyl‐L‐leucyl‐L‐aminosuccinyl‐L‐phenylalaninamide crystallizes in the orthorhombic space group P212121, with a = 6.214(3), b = 12.832(3), c = 33.094(4) Å, Z = 4. The structure was solved by direct methods using MULTAN 80 and refined to an R value of 0.055 for 1458 reflections. The bond lengths and angles are in good agreement with the standard values. The peptide backbone adopts a type II′ β‐bend conformation with a weak intramolecular hydrogen bond between the CO group of the leucyl residue and the C‐terminal NH2 group. In agreement with previous studies, this structure confirms the high propensity of aminosuccinyl peptides to adopt a type II′ β‐bend conformation. The role of this conformation in relation to the deamidation process in proteins is also discussed.
Synthesis and structural studies of N‐p‐toluensulfonyl cyclodipeptides
Authors: Calcagni A. , Lucente G. , Mazza F. , Pochetti G. , Rossi D. 
Published: December 2004

AbstractIn view of the chemical and structural interest of cyclopeptides bearing an electron withdrawing substituent directly bonded at the amide nitrogen atom, the two N‐p‐toluensulfonyl (N‐tosyl) derivatives cyclo[‐Phe(Tos)‐D‐Phe‐] (I) and cyclo[‐Phe(Tos)‐D‐Pro‐] (II) have been synthesized and their stereochemistry defined. The molecular structure of I, as determined by x‐ray diffraction analysis, is reported together with 1H‐nmr parameters indicating the preferred rotameric conformation in chloroform solution. The N‐tosyl group alters the geometry of the cyclodipeptide ring by lengthening both the NC bonds departing from the tosylated nitrogen and reducing the corresponding ring angle. The 6‐membered peptide ring adopts an unusual “sofa” conformation with the Tos‐Phe Cα atom deviating 0.230(3) Å out of the mean plane of the other five ring atoms. One of the two SO bonds forms a planar system that involves the tosylated nitrogen and the corresponding amide carbonyl. In the crystal, both the benzylic side chains are folded over the heterocyclic ring, whereas in chloroform solution, the benzylic side chain of the D‐Phe prefers an extended conformation.
Design and conformation of non‐Aib synthetic peptides enjoying alamethicin‐like ionophore activity
Authors: Molle G. , Duclohier H. , Dugast J.‐Y. , Spach G. 
Published: December 2004

AbstractAnalogues of alamethicin, a 20‐mer amphipathic helical peptide with ionophore activity, in the sequence of which all Aib residues were substituted by Ala (A1) or Leu (L1), were synthesized by the solid phase method, purified by high performance liquid chromatography and characterized by fast atomic bombardment mass spectrometry. Infrared and CD studies showed that A1 easily underwent a transconformation to β‐structure whereas L1 displayed a predominant α‐helical character, thus being a potential ionophore model. Its voltage‐dependent multistate activity in model membrance showed that Aib is not a requisite residue to observe an alamethicin‐like behavior. However, as the lifetime of the single channels was much shorter than for alamethicin, the peptide chain was lengthened by a Leu (LL1) or a Ser (SL1) residue. The last peptide gave an increased channel lifetime, but the design of other non‐Aib peptides, taking into account the hydroxyl C‐terminus and side‐chain interactions between helices in a barrel‐stave bundle, is desirable to approach more closely the alamethicin activity.
Ala analogues of the cyclolinopeptide A
Authors: Zanotti Giancarlo , Tancredi Teodorico , Rossi Filomena , Benedetti Ettore , Pedone Carlo , Temussi Pierandrea 
Published: December 2004

AbstractAnalogues of cyclolinopeptide A, due to the replacement of each amino acid in the Pro1‐Pro2‐Phe3‐Phe4 sequences with an L‐Ala residue, were synthesized by classical method in solution. Mixed anhydride and N,N′‐dicyclohexylcarbodiimide coupling methods have been used for the synthesis of both linear and cyclic peptides. The products were characterized by Rf values and uv spectra, as well as by fast atom bombardment spectroscopy.1H‐nmr studies on [Ala2] analogues are also reported. Preliminary data in CDCI3 solution, at low temperature, seems more promising.
Electron microscopy of native xanthan and xanthan exposed to low ionic strength
Authors: Stokke Bjørn T. , Smidsrød Olav , Elgsaeter Arnljot 
Published: December 2004

AbstractOptical rotation data indicate that xanthan can exist both in an ordered and a disordered conformation. Using molecular weights obtained from light scattering measurements and contour length distributions obtained from electron micrographs, we find that a native, filtered xanthan exposed to low salinity (< 10−4M NaCl) and subsequently returned to 0.1M NaCl has a highly elongated structure with a mass per unit length of 1950 ± 200 Dalton/nm. Our data thus suggest that the ordered conformation of this xanthan is double stranded. We find that native, filtered xanthan in 0.1M NH4Ac has a nearly similar structure, but exists in part as aggregates of varying shape and size. Electron micrographs of these xanthans in 10−4M NH4Ac (the disordered conformation) display a mixture of species ranging from unaggregated single‐ or perfectly matched double‐stranded species, to double‐stranded chains branching into its two subunits as well as double‐stranded chains with different degrees of mismatching. This study suggests that the perfectly matched antiparallel or parallel double‐stranded chain constitutes the lowest free energy state of the ordered conformation of xanthan in dilute aqueous solution.