bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of kindreds with parkinsonism and α‐synuclein genomic multiplications
Authors: Farrer Matt , Kachergus Jennifer , Forno Lysia , Lincoln Sarah , Wang Deng‐Shun , Hulihan Mary , Maraganore Demetrius , Gwinn‐Hardy Katrina , Wszolek Zbigniew , Dickson Dennis , Langston J. William 
Published: January 2004

AbstractGenomic triplication of the α‐synuclein gene recently has been associated with familial Parkinson's disease in the Spellman–Muenter kindred. Here, we present an independent family, of Swedish‐American descent, with hereditary early‐onset parkinsonism with dementia due to α‐synuclein triplication. Brain tissue available from affected individuals in both kindreds provided the opportunity to compare their clinical, pathological, and biochemical phenotypes. Of note, studies of brain mRNA and soluble protein levels demonstrate a doubling of α‐synuclein expression, consistent with molecular genetic data. Pathologically, cornu ammonis 2/3 hippocampal neuronal loss appears to be a defining feature of this form of inherited parkinsonism. The profound implications of α‐synuclein overexpression for idiopathic synucleinopathies are discussed.
Autosomal dominant acute necrotizing encephalopathy maps to 2q12.1‐2q13
Authors: Neilson Derek E. , Feiler Heidi S. , Wilhelmsen Kirk C. , Lynn Audrey , Eiben Robert M. , Kerr Douglas S. , Warman Matthew L. 
Published: January 2004

AbstractIn autosomal dominant acute necrotizing encephalopathy (ADANE), apparently healthy children develop necrotizing lesions in their thalami and brainstems in the course of febrile illnesses. We used DNA from affected subjects and obligate carriers to map ADANE to a 6.5Mb region on chromosome 2. Sequencing of four candidate genes in the interval (BCL2L11, ST6GalII, CHT1, and FLJ20019), involved in apoptosis, viral recognition, choline transport, and electron transport, showed no disease causing mutations.
Solution conformations of cyclosporins and magnesium‐cyclosporin complexes determined by vibrational circular dichroism
Authors: Bodack Louise A. , Freedman Teresa B. , Chowdhry Babur Z. , Nafie Laurence A. 
Published: January 2004

AbstractVibrational circular dichroism (VCD) spectroscopy was used to investigate the solution conformations of cyclosporins A, C, D, G, and H in CDCl3, in the amide I and NH/OH‐stretching regions, and their corresponding magnesium complexes in CD3CN, in the amide I region. VCD spectra are sensitive to the chiral arrangement of CO and NH bonds in this cyclic undecapeptide. Calculations of molecular geometries, as well as IR and VCD intensities of model cyclosporin fragments that include the intramolecular hydrogen bonds of the crystal conformations of cyclosporins A and H (CsA and CsH), were carried out at the density functional theory (DFT; BPW91 functional/6‐31G* basis set) level. The good agreement between IR and VCD spectra from experiment and DFT calculations provides evidence that the crystal conformation of CsA is dominant in CDCl3 solution; CsH, however, assumes both an intramolecularly hydrogen‐bonded crystal conformation and more open forms in solution. Comparisons of the experimental and calculated VCD spectra in the NH/OH‐stretching region of the noncomplexed cyclosporins indicate that conformers with both free and hydrogen‐bonded NH and OH groups are present in solution. Differences between the IR and VCD spectra for the metal‐free and magnesium‐complexed cyclosporins are indicative of strong interactions between cyclosporins and magnesium ions. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 163–177, 2004
The ribbon of hydrogen bonds in globular proteins. IV. The example of the papain family
Authors: Peters David , Peters Jane 
Published: January 2004

AbstractA study of the role of the hydrogen‐bonding side chains in the ribbon of hydrogen bonds in globular proteins, using the papain family as an example, suggests that these side chains may be divided into three categories depending on their position in the molecule. In the first category, they form part of the local ribbon, in the second they form part of the ribbon at a site remote along the main chain, and in the third they play no role in the formation of the ribbon. The second case is particularly interesting because it provides a natural mechanism for the formation of the tertiary structure of the globular proteins. The results suggest that the robustness of the globular proteins towards mutations arises from the fact that many mutations that involve hydrogen‐bonding side chains either leave the hydrogen bonding of the ribbon essentially unchanged or their hydrogen bonding plays no part in the formation of the ribbon in the first place. The results show that it is possible to obtain the ribbon of hydrogen bonds for a family of proteins whose data set's are of intermediate quality by studying the ribbons of several members of such a family and then taking an average over the different partial ribbons to create a standard ribbon of hydrogen bonds for the family as a whole. This method is used here to derive the standard ribbon for the papain family with papain itself, actinidin, and human liver cathepsin B as the representatives of the family. All three members of the family fit the standard ribbon with an accuracy of 85–91%. This result opens up the use of this technique for the study of a large number of globular proteins whose recorded data sets are of intermediate quality. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 178–191, 2004
Molecular dynamics simulations of papilloma virus E2 DNA sequences: Dynamical models for oligonucleotide structures in solution
Authors: Byun K. Suzie , Beveridge D. L. 
Published: January 2004

AbstractThe specificity of papilloma virus E2 protein–DNA binding depends critically upon the sequence of a region of the DNA not in direct contact with the protein, and represents one of the simplest known examples of indirect readout. A detailed characterization of this system in solution is important to the further investigation hypothesis of a structural code for DNA recognition by regulatory proteins. In the crystalline state, the E2 DNA oligonucleotide sequence, d(ACCGAATTCGGT), exhibits three different structural forms. We report herein studies of the structure of E2 DNA in solution based on a series of molecular dynamics (MD) simulations including counterions and water, utilizing both the canonical and various crystallographic structures as initial points of departure. All MDs converged on a single dynamical structure of d(ACCGAATTCGGT) in solution. The predicted structure is in close accord with two of the three crystal structures, and indicates that a significant kink in the double helix at the central ApT step in the other crystal molecule may be a packing effect. The dynamical fine structure was analyzed on the basis of helicoidal parameters. The calculated curvature in the sequence was found to originate primarily from YPR steps in the regions flanking the central AATT tract. In order to study the role of structural adaptation of the DNA in the binding process, a subsequent simulation on the 16‐mer cognate sequence d(CAACCGAATTCGGTTG) was initiated from the crystallographic coordinates of the bound DNA in the crystal structure of the protein DNA complex. MD simulations starting with the protein‐bound form relaxed rapidly back to the dynamical structure predicted from the previous simulations on the uncomplexed DNA. The MD results show that the bound form E2 DNA is a dynamically unstable structure in the absence of protein, and arises as a consequence of both structural changes intrinsic to the sequence and induced by the interaction with protein. © 2003 Wiley Periodicals, Inc. Biopolymers 73:369–379, 2004
DNA fine structure and dynamics in crystals and in solution: The impact of BI/BII backbone conformations
Authors: Djuranovic D. , Hartmann B. 
Published: January 2004

AbstractSugar–phosphate backbone conformations are an important structural element for a complete understanding of specific recognition in nucleic acid–protein interactions. They can be involved both in early stages of target discrimination and in structural adaptation upon binding. In the first part of this study, we have analyzed high‐resolution structures of double‐stranded B‐DNA either isolated or bound to proteins, and explored the impact of both the standard BI and the unusual BII phosphate backbone conformations on neighboring sugar puckers and on selected helical parameters. Correlations are found to be similar for free and bound DNA, and in both categories, the possible facing backbone conformations (BI.BI, BI.BII, and BII.BII) define well‐characterized substates in the B‐DNA conformational space. Notably, BII.BII steps are characterized by specific, and sequence‐independent, structural effects involving reduced standard deviations for almost all conformational parameters. In the second part of this work, we analyze four 10 ns molecular dynamics simulations in explicit solvent on the DNA targets of NF‐κB and bovine papillomavirus E2 proteins, highlighting the multiplicity of backbone dynamical behavior. These results show sequence effects on the percentages of BI and BII conformers, the preferential state of facing backbones, the occurrence of coupled transitions. The backbone states can consequently be seen as a mechanism for transmitting information from the bases to the phosphate groups and thus for modulating the overall structural properties of the target DNA. © 2003 Wiley Periodicals, Inc. Biopolymers 73:356–368, 2004
Packaging double‐helical DNA into viral capsids
Authors: LaMarque Jaclyn C. , Le Thuc‐vy L. , Harvey Stephen C. 
Published: January 2004

AbstractDNA packaging in bacteriophage P4 has been examined using a molecular mechanics model with a reduced representation containing one pseudoatom per turn of the double helix. The model is a discretized version of an elastic continuum model. The DNA is inserted piecewise into the model capsid, with the structure being reoptimized after each piece is inserted. Various optimization protocols were investigated, and it was found that molecular dynamics at a very low temperature (0.3 K) produces the optimal packaged structure. This structure is a concentric spool, rather than the coaxial spool that has been commonly accepted for so many years. This geometry, which was originally suggested by Hall and Schellman in 1982 (Biopolymers Vol. 21, pp. 2011–2031), produces a lower overall elastic energy than coaxial spooling. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 348–355, 2004
Volumetric properties of the formation of double stranded DNA: A nearest‐neighbor analysis
Authors: Dubins David N. , Macgregor Robert B. 
Published: January 2004

AbstractThe kinetics of the helix‐coil transition have been studied by performing UV‐monitored melting and reannealing curves of DNA and analyzing the resultant hysteresis between these curves. The analysis assumes a single‐step bimolecular transition with duplex formation defined as the forward reaction. Volume parameters of the helix‐coil transition were obtained by measuring the pressure dependence of the rate constants from 5–200 MPa. The data were interpreted in terms of several possible nearest‐neighbor models, ranging from one to eleven parameters. Twenty‐four oligonucleotide duplexes 22 base pairs in length were used to solve for individual nearest‐neighbor activation volumes and transition volumes. Statistically, the most valid fit of the volumetric data was obtained with a six‐parameter model in which the directionality of the dinucleotide steps is not considered, for example, 5′AG/CT is the same as 5′GA/TC. The resultant transition volumes at 48°C ranged from −7.1 ± 0.8 mL/mol (GC/CG) to +2.9 ± 0.3 mL/mol (AA/TT). The success of the six‐parameter model suggests that the relative size of the nearest‐neighbor dinucleotides is the most important factor determining the magnitude of the volumetric parameters. The finding that the magnitude of the volumetric parameters correlates with the change in the solvent accessible surface area of the bases during the helix‐coil transition corroborates this hypothesis. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 242–257, 2004
Temperature and pressure effects on conformational equilibria of alanine dipeptide in aqueous solution
Authors: Takekiyo Takahiro , Imai Takashi , Kato Minoru , Taniguchi Yoshihiro 
Published: January 2004

AbstractWe investigated the temperature and pressure effects on conformational equilibria of N‐acetyl‐L‐alanine‐N′‐methylamide (AAlaMA) in aqueous solution by Raman spectroscopy. Scattering intensities in the skeletal stretching mode of AAlaMA in aqueous solution were decomposed into some component bands by the spectra analysis. Our results indicate that each component band for AAlaMA adopts not only the PII and αR conformations but also the C7eq conformation. From temperature and pressure dependencies of the band intensities, we determined the enthalpy differences and the volume differences between the conformers. The C7eq conformer is enthalpically most stable due to the intramolecular hydrogen bond. The partial molar volume of the C7eq conformer is the smallest through the solvent‐exclusion effect rather than the solute‐solvent electrostatic interaction effect. © 2004 Wiley Periodicals, Inc. Biopolymers 73: 283–290, 2004
Conformational and structural analysis of the equilibrium between single‐ and double‐strand β‐helix of a D,L‐alternating oligonorleucine
Authors: Navarro E. , Fenude E. , Celda B. 
Published: January 2004

AbstractAlternating sequences of D and L residues in peptides are directly related to the formation of several kinds of regular helical conformations usually called β‐helices. The major feature of these structures is that they can be associated with the transmembrane ion‐conducting channel activity in some natural antibacterial peptides. The study of alternating D,L synthetic peptides is critical to understand how factors such as surrounding media, main chain length, type of side chain and terminal groups, among others, can determine the adoption of a specific kind of β‐helix. Early studies pointed out that the peptides Boc(D‐NLeuL‐NLeu)6D‐MeNLeL‐NleD‐NleL‐NleOMe (Boc: tert‐butyloxycarbonyl) and BocL‐Nle(D‐NleL‐Nle)5D‐MeNleL‐NleD‐NleL‐NleOMe adopt in chloroform a unique detectable conformation single β4.4‐ and double β5.6↑↓‐helix, respectively. The influence of terminal groups on the final stable conformation of N‐formylated peptides has been studied in this work. The initial basic NMR data analysis of a synthetic alternating D,L‐oligopeptide with ten norleucines, N‐methylated on the residue 7 and having HCO and OMe as terminal groups clearly indicates the coexistence of two different conformations in equilibrium. NMR data and molecular dynamics calculations point to a dimeric antiparallel β‐helix structure β5.6↑↓ for the main conformation. On the other hand, NMR data suggest a single β‐helix structure β4.4 for the second conformation. Finally, a thermodynamic analysis of the equilibrium between both conformations has been carried out by one‐dimensional NMR measurements at ten different temperatures. The temperature at which 50% of dimer conformation is dissociated is 319 K. In addition, the dimer–monomer equilibrium curve obtained shows a ΔG>0 for the whole range of studied temperatures, and its behavior can be considered similar to the thermodynamic denaturation protein processes. © 2003 Wiley Periodicals, Inc. Biopolymers 73:229–241, 2004
Identification of possible kinetically significant anion‐binding sites in human serum transferrin using molecular modeling strategies
Authors: Amin Elizabeth Ambrose , Harris Wesley R. , Welsh William J. 
Published: January 2004

AbstractCertain anions have been shown experimentally to influence the rate of iron release from human serum transferrin (HST), implying the existence of one or more allosteric kinetically significant anion‐binding (KISAB) sites on or near the surface of the protein. A rank‐ordered selection of potential HST KISAB sites has been obtained using a novel three‐stage molecular modeling strategy. The crystal structure of HST (1A8E.pdb) was first subjected to a heuristic analysis, in which positively charged and hydrogen‐bonding residues on or near the surface of the protein were identified. In this stage, a preliminary electrostatic potential map was also calculated, yielding six preliminary sites. Next, energy‐grid calculations were conducted in order to identify anion–protein interaction energy minima, which resulted in the inclusion of three additional sites. Finally, three anions already shown experimentally to demonstrate varied effects on HST iron‐release kinetics were placed at each potential site; molecular dynamics and molecular mechanics calculations were performed in order to elucidate the hydrogen‐bonding environment around each anion of the protein as well as to calculate anion–protein‐binding energies. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 205–215, 2004
Exploring the interaction of the surfactant N‐terminal domain of γ‐Zein with soybean phosphatidylcholine liposomes
Authors: Kogan Marcelo J. , López Olga , Cocera Mercè , López‐Iglesias Carmen , De la Maza Alfonso , Giralt Ernest 
Published: January 2004

AbstractZeins are maize storage proteins that accumulate inside large vesicles called protein bodies. γ‐Zein lines the inner surface of the protein body membrane, and its N‐terminal, proline‐rich, repetitive domain with the sequence (VHLPPP)8 appears to be necessary for the accumulation of the protein within the organelle. Synthetic (VHLPPP)8 adopts an amphipathic polyproline II conformation and forms cylindrical micelles in aqueous solution. Here we explore the interaction of (VHLPPP)8 with soybean phosphatidylcholine unilamellar lipid vesicles and examine its effect on the stability and permeability of the liposome membrane. The amphipathic N‐terminal domain of γ‐zein interacts with the membrane and assembles to form extended domains over the phospholipid membrane. The interaction between the peptide and the membrane increases the stability and permeability of the liposome membrane. The spontaneous amphipathic aggregation of (VHLPPP)8 on the membrane suggests a mechanism of γ‐zein deposition inside maize protein bodies. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 258–268, 2004
DNA melting profiles from a matrix method
Authors: Poland Douglas 
Published: January 2004

AbstractIn this article we give a new method for the calculation of DNA melting profiles. Based on the matrix formulation of the DNA partition function, the method relies for its efficiency on the fact that the required matrices are very sparse, essentially reducing matrix multiplication to vector multiplication and thus making the computer time required to treat a DNA molecule containing N base pairs proportional to N2. A key ingredient in the method is the result that multiplication by the inverse matrix can also be reduced to vector multiplication. The task of calculating the melting profile for the entire genome is further reduced by treating regions of the molecule between helix‐plateaus, thus breaking the molecule up into independent parts that can each be treated individually. The method is easily modified to incorporate changes in the assignment of statistical weights to the different structural features of DNA. We illustrate the method using the genome of Haemophilus influenzae. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 216–228, 2004
Excluded volume effect in unzipping DNA with a force
Authors: Lam Pui‐Man , Levy J.C.S. , Huang Hanchen 
Published: January 2004

AbstractA double stranded DNA molecule when pulled with a force acting on one end of the molecule can become either partially or completely unzipped depending on the magnitude of the force F. For a random DNA sequence, the number M of unzipped base pairs goes as M≈(F − Fc)−2 and diverges at the critical force Fc with an exponent χ = 2. We find that when excluded volume effect is taken into account for the unzipped part of the DNA, the exponent χ = 2 is not changed but the critical force Fc is changed. The force versus temperature phase diagram depends on only two parameters in the model, the persistence length and the denaturation temperature. Furthermore a scaling form of the phase diagram can be found. This scaling form is parameter independent and depends only on the spatial dimension. It applies to all DNA molecules and should provide a useful framework for comparison with experiments. © 2004 Wiley Periodicals, Inc. Biopolymers 73: 293–300, 2004
Molecular dynamics simulations of a guaiacyl β‐O‐4 lignin model compound: Examination of intramolecular hydrogen bonding and conformational flexibility
Authors: Besombes Stéphane , Mazeau Karim 
Published: January 2004

AbstractThe dynamical conformational behavior of a guaiacyl β‐O‐4 lignin model compound has been investigated by molecular simulations. The potential energy surface of the molecule in vacuum has been examined by means of an adiabatic map, showing a large accessible conformational space with multiple energy minima separated by low barriers. Molecular dynamics simulations have been performed in vacuum and with explicit solvent molecules for 10 and 2.1 ns, respectively. Molecular dynamics trajectories recorded in vacuum have shown the molecule to be flexible and to visit a large number of conformations. Many intramolecular H‐bonds have been observed, existing for more than 90% of the total simulation time. The presence of explicit solvent molecules induces a significant broadening of some regions of the accessible conformational space and also largely reduces the statistical significance of intramolecular H‐bonding. Intramolecular H‐bonds observed in vacuum do not persist significantly and are preferentially exchanged with intermolecular H‐bonds to the surrounding solvent molecules. The theoretical results are in good agreement with experimental NMR data that do not support the existence of strong and persistent intramolecular H‐bonds in solution but instead indicate that H‐bonds to solvent predominate. Finally, both molecular modeling and NMR approaches predict the guaiacyl β‐O‐4 structure to be flexible and indicate that intramolecular H‐bonds are not strong and persistent enough to confer rigidity to the molecule in solution. © 2004 Wiley Periodicals, Inc. Biopolymers 73: 301–315, 2004
Structural similarity of E. coli 5S rRNA in solution and within the ribosome
Authors: Skibinska Lidia , Banachowicz Ewa , Gapiński Jacek , Patkowski Adam , Barciszewski Jan 
Published: January 2004

AbstractThe article presents translational and rotational diffusion coefficients of 5S rRNA determined experimentally by the method of dynamic light scattering (DLS) and its comparison with the values predicted for different models of this molecule. The tertiary structure of free 5S rRNA was proposed on the basis of the atomic structures of the 5S rRNA from E. coli and H. marismortui extracted from the ribosome. A comparison of the values of DT, τR, and Rg predicted for different models with experimental results for the free molecule in solution suggests that free 5S rRNA is less compact than that in the complex with ribosomal proteins. In general, the molecules of 5S rRNA consist of three domains: a short one and two longer ones. As follows from a comparison of the results of our simulations with experimental values, in the molecule in solution the two closest helical fragments of the longer domains remain collinear, whereas the short domain takes a position significantly deviated from them. © 2004 Wiley Periodicals, Inc. Biopolymers 73: 316–325, 2004