bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of protein–ligand binding site polarizability
Authors: Nayeem Akbar , Krystek Stanley , Stouch Terry 
Published: September 2003

AbstractElectronic polarizability, an important physical property of biomolecules, is currently ignored in most biomolecular calculations. Yet, it is widely believed that polarization could account for a substantial fraction of the total nonbonded energy of a system. This belief is supported by studies of small complexes in vacuum. This perception is driving the development of a new class of polarizable force fields for biomolecular calculations. However, the quantification of this term for protein–ligand complexes has never been attempted. Here we explore the polarizable nature of protein–ligand complexes in order to evaluate the importance of this effect. We introduce two indexes describing the polarizability of protein binding sites. These we apply to a large range of pharmaceutically relevant complexes. We offer a recommendation of particular complexes as test systems with which to determine the effects of polarizability and as test cases with which to test the new generation of force fields. Additionally, we provide a tabulation of the amino acid composition of these binding sites and show that composition can be specific for certain classes of proteins. We also show that the relative abundance of some amino acids is different in binding sites than elsewhere in a protein's structure. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 201–211, 2003
Analysis of DNA bending by transient electric birefringence
Authors: Lu Yongjun , Weers Brock D. , Stellwagen Nancy C. 
Published: September 2003

AbstractTransient electric birefringence has been used to analyze DNA bending in six restriction fragments containing 171, 174, 207, 263, 289, and 471 bp in three different low ionic strength buffers. The target fragments contain sequences corresponding to the apparent bend centers in pUC19 and Litmus 28, previously identified by the circular permutation assay (Strutz, K.; Stellwagen, N. C. Electrophoresis 1996, 17, 989–995). The target fragments migrate anomalously slowly in polyacrylamide gels and exhibit birefringence relaxation times that are shorter than those of restriction fragments of the same size, taken from nonbent regions of the same plasmids. Apparent bend angles ranging from 30° to 41° were calculated for the target fragments by τ‐ratio method. The bend angles of four of the target fragments were independent of temperature from 4°C to 20°C, but decreased when the temperature was increased to 37°C. The bend angles of the other two target fragments were independent of temperature over the entire range examined, 4°–37°C. Hence, the thermal stability of sequence‐dependent bends in random‐sequence DNA is variable. The bend angles of five of the six target fragments were independent of the presence or absence of Mg2+ ions in the solution, indicating most of the target fragments were stably bent or curved, rather than anisometrically flexible. Restriction fragments containing 219 and 224 bp, with sequences somewhat offset from the sequence of the 207 bp fragment, were also studied. Comparison of the τ‐ratios of these overlapping fragments allowed both the bend angle and bend position to be independently determined. These methods should be useful for analyzing sequence‐dependent bending in other random‐sequence DNAs. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 270–288, 2003
Brownian dynamics simulation of helix‐capping motifs
Authors: Shen Tongye , Wong Chung F. , McCammon J. Andrew 
Published: September 2003

AbstractHelix ‐capping motifs are believed to play an important role in stabilizing α‐helices and defining helix start and stop signals. We performed microsecond scale Brownian dynamics simulations to study ten XAAD sequences, with X = (A,E,I,L,N,Q,S,T,V,Y), to examine their propensity to form helix capping motifs and correlate these results with those obtained from analyzing a structural database of proteins. For the widely studied capping box motif S**D, where the asterisk can be any amino acid residue, the simulations suggested that one of the two hydrogen bonds proposed earlier as a stabilizing factor might not be as important. On the other hand, side‐chain interactions between the capping residue and the third residue downstream on the polypeptide chain might also play a role in stabilizing this motif. These results are consistent with explicit‐solvent molecular dynamics simulations of two capping box motifs found in the proteins BPTI and α‐dendrotoxin. Principal component analysis of the SAAD trajectory showed that the first three principal components, after those corresponding to translational‐rotational motion were removed, accounted for more than half of the conformational fluctuations. The first component separated the conformational space into two parts with the all‐helical conformation and the capping box motif lying largely in one part. The second component, on the other hand, could be used to describe conformational transitions between the all‐helical form and the capping box motif. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 252–259, 2003
Cation effects on swelling of κ‐carrageenan: A photon transmission study
Authors: Kara Selim , Tamerler Candan , Pekcan Önder 
Published: September 2003

AbstractSwelling behavior of κ‐carrageenan gels in water and KCl solutions was investigated by photon transmission experiments following the preparation of gels in the presence and absence of externally added K+ ion as a gel promoting agent. Transmitted photon intensity, Itr, increased continuously during swelling depending on the carrageenan and ion content in the gel. This increase in Itr was modeled using the Li–Tanaka equation. Both the experimental work and the model showed that the swelling of low carrageenan and ion content gels took less time than that of high ion content gels. It is confirmed that double helices in a swollen gel move much faster in pure water than in KCl solution during swelling processes. Swelling time constants, τ1, and collective diffusion coefficients, Do, were measured for the gels swollen in water and KCl solutions. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 240–251, 2003
MM3 potential energy surfaces of trisaccharides. II. Carrageenan models containing 3,6‐anhydro‐D‐galactose
Authors: Stortz Carlos A. , Cerezo Alberto S. 
Published: September 2003

AbstractThe adiabatic potential energy surfaces (PES) of six trisaccharides—namely 3,6‐An‐α‐D‐Galp‐(1→3)‐β‐D‐Galp‐(1→4)‐3,6‐An‐α‐D‐Galp, β‐D‐Galp‐(1→4)‐3,6‐An‐α‐D‐Galp‐(1→3)‐β‐D‐Galp, and their derivatives sulfated on positions 2 and 4 of the β‐galactose unit—were obtained using the MM3 force field. Each PES was described by a single contour map for which the energy is plotted against the two ψ glycosidic angles, given the small variations of the ϕ glycosidic torsional angle in the low‐energy regions of disaccharide maps. In five of the six examples, the surfaces are those expected from the maps of the disaccharidic repeating units of carrageenans, with less important factors altering the additive effect of both linkages. However, when a sulfate group is present on C2 of a β‐galactose reducing end, a new low‐energy minimum in a different region is produced, originated in a hydrogen bond between the first and third monosaccharidic moieties of the trisaccharide. The flexibility of the β‐linkages is nearly identical to that in their disaccharide counterparts, while that of the α‐linkages is slightly reduced, independent of their presence closer or further away from the reducing end. A fair agreement is observed between the x‐ray fiber diffraction analysis for a κ‐carrageenan double helix and the surfaces obtained for the trisaccharide analogs of that polymer. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 227–239, 2003
Conformational constraints of tyrosine in protein tyrosine kinase substrates: Information about preferred bioactive side‐chain orientation
Authors: Ruzza Paolo , Calderan Andrea , Donella‐Deana Arianna , Biondi Barbara , Cesaro Luca , Osler Alessio , Elardo Stefano , Guiotto Andrea , Pinna Lorenzo A. , Borin Gianfranco 
Published: September 2003

AbstractThe side‐chain orientation of a tyrosine residue located in a peptide, which is an excellent substrate of Syk tyrosine kinase (A. M. Brunati, A. Donella‐Deana, M. Ruzzene, O. Marin, L. A. Pinna, FEBS Letters, 1995, Vol. 367, pp. 149–152), was fixed in the gauche (+) or gauche (−) conformation by using the 7‐hydroxy‐1,2,3,4‐tetrahydro isoquinoline‐3‐carboxylic (Htc) structure. The tyrosine trans conformation was blocked by using an aminobenzazepine‐type (Hba) structure. The proposed side‐chain orientations were confirmed by the analysis of the 1H‐NMR parameters: chemical shifts, coupling constants, and nuclear Overhauser effects to the tyrosine constraints in the different analogs. This “rotamer scan” of the phosphorylatable residue allowed us to generate optimal substrates in terms of both phosphorylation efficiency and selectivity for Syk tyrosine kinase. In contrast, these conformationally restricted tyrosine analogs were not tolerated by the Src‐related tyrosine kinases Lyn and c‐Fgr. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 478–488, 2003
13C CPMAS NMR studies of the elastin‐like polypeptide (LGGVG)n
Authors: Kumashiro Kristin K. , Kurano Tracie L. , Niemczura Walter P. , Martino Marica , Tamburro Antonio M. 
Published: September 2003

AbstractThe elucidation of structure‐function relationships in insoluble elastin is often approached using elastin‐like polypeptides. In this manner, the characterization of the different regions in this extensive biopolymer may be facilitated in a “piece‐wise” manner. Our solid‐state NMR experiments indicate that (LGGVG)n has structural similarities to elastin and some elastin peptides, providing support for the utility of the mimetic peptides. Furthermore, previous NMR and CD studies indicated that the structure of the elastin‐like polypeptide (LGGVG)n in solution is best described as a “conformational ensemble” with a mixture of type I and II β‐turns, in addition to unfolded regions. Our data indicate that the peptide does not adopt a single conformation in the solid state, lending further support to models for elastin that involve significant conformational heterogeneity. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 221–226, 2003
Peptide‐bond modification for metal coordination: Peptides containing two hydroxamate groups
Authors: Ye Yunpeng , Liu Min , Kao Jeff L.‐K. , Marshall Garland R. 
Published: September 2003

AbstractPeptide‐bond modification via N‐hydroxylation has been explored as a strategy for metal coordination to induce conformational rigidity and orient side chains for specific molecular recognition. N‐Hydroxyamides were prepared by reacting N‐benzyloxyamino acid esters or amides with Fmoc–AA–Cl/AgCN (Fmoc: 9‐fluorenylmethoxycarbonyl; AA: amino acid) in toluene or Fmoc–AA/HATU/DIEA in DMF (HATU: O‐(7‐azabenzotriazol‐lyl)‐1,1,3,3‐tetramethyluronium hexafluorophosphate; DIEA: N,N‐diisopropylethylamine; DMF: N,N‐dimethylformamide), followed by deblocking of benzyl protecting groups. Novel linear and cyclic N,N′‐dihydroxypeptides were efficiently assembled using Fmoc chemistry in solution and/or on a solid support. As screened by electrospray ionization–mass spectroscopy (ESI‐MS), high iron‐binding selectivity and affinity were attainable. Compounds having a spacer of two α‐amino acids between the amino acids bearing the two hydroxamates, i.e., a spacer of 8 atoms, generated 1:1 iron complex species in the gas phase. Moreover, high performance liquid chromatography (HPLC), uv/vis, and 1H‐NMR analyses provided direct evidence for complex formations in solution. Significantly, the representative compound cyclo(Leu–Ψ[CON(OH)]–Phe–Ala–Pro)2 (P8) may serve as a robust metal‐binding scaffold in construction of a metal‐binding library for versatile metal‐mediated molecular recognition. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 489–515, 2003
Study of electrostatic potential surface distribution of wild‐type plastocyanin Synechocystis solution structure determined by homonuclear NMR
Authors: Monleón Daniel , Celda Bernardo 
Published: September 2003

AbstractPlastocyanin is a small (∼10 kDa), type I blue copper protein that works as an electron donor to photosystem I from cytochrome f in both chloroplast systems and in some strains of cyanobacteria. Comparative studies of the kinetic mechanisms of plastocyanins in different organisms show that the electron transfer from photosystem I happens by simple collision in cyanobacteria but through a intermediate transition complex in green algae and superior plants. Previous work has proved that this effect cannot be explained by structural variations across the different plastocyanins but it can be explained by differences in the electrostatic potential distribution at the protein surface. In that case, minor conformational errors at the amino acid side chain level may imply an important effect in the electrostatic potential distribution calculation. In this work we present a high resolution study of side chain conformation by homonuclear NMR for the reduced wild‐type plastocyanin Synechocystis using intensity ratios for 2D‐NOESY and 2D‐H,H‐TOCSY cross peaks at different mixing times. We also present the corresponding comparison with different plastocyanin structures and the effect in the electrostatic potential distribution at the protein surface. We discuss the importance of indirect J‐coupling information from TOCSY‐type experiments as complement for intraresidue distances derived from NOESY experiments in the determination of side chain orientation and stereo‐specific assignments. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 212–220, 2003
Biosynthesis and biophysical analysis of domains of a yeast G protein‐coupled receptor
Authors: Arevalo Enrique , Estephan Racha , Madeo Jenifer , Arshava Boris , Dumont Mark , Becker Jeffrey M. , Naider Fred 
Published: September 2003

AbstractThe α‐factor receptor(Ste2p) is required for the sexual conjugation of the yeast Saccharomyces cerevisiae. Ste2p belongs to the G protein‐coupled receptor (GPCR) family sharing a common heptahelical transmembrane structure. Biological synthesis of regions of Ste2p fused to a leader protein in Escherichia coli yielded milligram quantities of polypeptides that corresponded to one or two transmembrane domains. Fusion proteins were characterized by polyacrylamide gel electrophoresis, high performance liquid chromatography, and mass spectrometry. CD studies on the fusion proteins in trifluoroethanol:water mixtures indicated the existence of α‐helical structures in the single‐ and the double‐transmembrane domains. NMR experiments were performed in CDCl3:CD3OH:H2O (4:4:1) on the 15N‐labeled single‐transmembrane peptide showing a clear dispersion of the nitrogen–amide proton correlation cross peaks indicative of a high‐purity, uniformly labeled molecule. The results indicate that single‐ and double‐transmembrane domains of a GPCR can be produced by biosynthetic methods in quantities and purity sufficient for biophysical studies. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 516–531, 2003
Solid‐phase synthesis of C‐terminal modified peptides
Authors: Alsina Jordi , Albericio Fernando 
Published: September 2003

AbstractSolid‐phase synthesis of biomolecules, of which peptides are the principal example, is well established. However, synthetic peptides containing modifications at the carboxy termini are often desired because of their potential therapeutic properties. As a result, there is a necessity for effective solid‐phase strategies for the preparation of peptides with C‐terminal end groups other than the usual carboxylic acid and carboxamide functionalities. The present article primarily reviews literature reports on methods for solid‐phase synthesis of C‐terminal modified peptides. In addition, general information about biological activities and/or synthetic applications of each individual class of peptide is also provided. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 454–477, 2003
ICESEE: A tool for developing engineering courseware
Authors: Ochoa Sergio F. , Pino José A. , Baloian Nelson , Fuller David A. 
Published: September 2003

AbstractIn this article, a computer tool is introduced to support courseware building and evolution in computer science and engineering education. The tool is intended to fulfill requirements, which are typical of this area of education. The tool has been implemented and initially tested. Instructors and students have been satisfied with the tool, therefore, indicating encouraging results. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 11: 53–66, 2003; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10032
Development of web‐based engineering numerical software (WENS) using MATLAB: Applications to linear algebra
Authors: Kim Albert S. , Park Chanho , Park Si‐Hwan 
Published: September 2003

AbstractIn this article, we present Web‐based Engineering Numerical Software (WENS) developed using MATLAB and its Web Server Toolbox (WST) in order to provide basic solution tools in linear algebra, including eigenvalue problems, which are extensively used in engineering applications and education. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 11: 67–74, 2003; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10038
An online thermodynamics courseware
Authors: Ngo C. C. , Lai F. C. 
Published: September 2003

AbstractThis article presents an online Thermodynamics courseware and how it can be used to enhance the learning experience of students. The courseware has been developed to present the materials in a dynamic and interactive fashion. It also includes a review section to help students in the preparation of the Fundamentals of Engineering (FE) Exam. Since its first implementation in summer 2000, this courseware has received overwhelming response from our students. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 11: 75–82, 2003; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10039
A web‐based 2D structural analysis educational software
Authors: Almeida Barretto Saulo Faria , Piazzalunga Renata , Ribeiro Viviane Guimarães 
Published: September 2003

AbstractThis paper describes an educational software developed to be helpful to undergraduate engineering students when learning with structural analysis. The software enables the user to analyze plane‐framed structures, under static or dynamic loading, and it was fully implemented by using web technology. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 11: 83–92, 2003; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10040
Neuro‐Lab: A highly reusable software‐based environment to teach artificial neural networks
Authors: García Roselló Emilio , García Pérez‐Schofield José B. , González Dacosta Jacinto , Pérez‐Cota Manuel 
Published: September 2003

AbstractIt is increasingly usual to find notions of artificial neural networks (ANNs) included in the curricula of many engineering studies. In this article, we present Neuro‐Lab, a simulation software to teach basic concepts of ANNs to undergraduate students of the Computer Engineering School in the University of Vigo (Spain). Neuro‐Lab was designed with the aim of offering a very easy‐to‐use user interface, support of exploratory learning activities, and also high reusability. This feature allows for an easy extension, integration, and interoperation of the software with other applications. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 11: 93–102, 2003; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10042
Flexible Adaptations in the Structure of the tRNA‐Modifying Enzyme tRNA–Guanine Transglycosylase and Their Implications for Substrate Selectivity, Reaction Mechanism and Structure‐Based Drug Design
Authors: Brenk Ruth , Stubbs Milton T. , Heine Andreas , Reuter Klaus , Klebe Gerhard 
Published: September 2003

AbstractThe enzyme tRNA–guanine transglycosylase (TGT, EC 2.4.2.29) catalyses a base‐exchange reaction that leads to anticodon modifications of certain tRNAs. The TGT enzymes of the eubacteria Zymomonas mobilis (Z. mobilis TGT) and Escherichia coli (E. coli TGT) show a different behaviour in the presence of competitive inhibitors. The active sites of both enzymes are identical apart from a single conservative amino acid exchange, namely Tyr106 of Z. mobilis TGT is replaced by a Phe in E. coli TGT. Although Tyr106 is, in contrast to Phe106, hydrogen bonded in the ligand‐free structure, we can show by a mutational study of TGT(Y106F) that this is not the reason for the different responses upon competition. The TGT enzymes of various species differ in their substrate selectivity. Depending on the applied pH conditions and/or induced by ligand binding, a peptide‐bond flip modulates the recognition properties of the substrate binding site, which changes between donor and acceptor functionality. Furthermore interstitial water molecules play an important role in these adaptations of the pocket. The flip of the peptide bond is further stabilised by a glutamate residue that operates as general acid/base. An active‐site aspartate residue, presumed to operate as a nucleophile through covalent bonding during the base‐exchange reaction, shows different conformations depending on the nature of the bound ligand. The induced‐fit adaptations observed in the various TGT complex structures by multiple crystal‐structure analyses are in agreement with the functional properties of the enzyme. In consequence, full understanding of this plasticity can be exploited for drug design.
Structural Investigation of a High‐Affinity MnIIBinding Site in the Hammerhead Ribozyme by EPR Spectroscopy and DFT Calculations. Effects of Neomycin B on Metal‐Ion Binding
Authors: Schiemann Olav , Fritscher Jörg , Kisseleva Natalja , Sigurdsson Snorri Th. , Prisner Thomas F. 
Published: September 2003

AbstractElectron paramagnetic resonance spectroscopy and density functional theory methods were used to study the structure of a single, high‐affinity MnIIbinding site in the hammerhead ribozyme. This binding site exhibits a dissociation constantKdof 4.4 μMin buffer solutions containing 1 MNaCl, as shown by titrations monitored by continuous wave (cw) EPR. A combination of electron spin echo envelope modulation (ESEEM) and hyperfine sublevel correlation (HYSCORE) experiments revealed that the paramagnetic manganese(II) ion in this binding site is coupled to a single nitrogen atom with a quadrupole coupling constantκof 0.7 MHz, an asymmetry parameterηof 0.4, and an isotropic hyperfine coupling constant ofAiso(14N)=2.3 MHz. All three EPR parameters are sensitive to the arrangement of the MnIIligand sphere and can therefore be used to determine the structure of the binding site. A possible location for this binding site may be at the G10.1, A9 site found to be occupied by MnIIin crystals (MacKay et al., Nature1994, 372,68 and Scott et al., Science1996, 274,2065). To determine whether the structure of the binding site is the same in frozen solution, we performed DFT calculations for the EPR parameters, based on the structure of the MnIIsite in the crystal. Computations with the BHPW91 density function in combination with a 9s7p4d basis set for the manganese(II) center and the Iglo‐II basis set for all other atoms yielded values ofκ(14N)=+0.80 MHz,η=0.324, andAiso(14N)=+2.7 MHz, in excellent agreement with the experimentally obtained EPR parameters, which suggests that the binding site found in the crystal and in frozen solution are the same. In addition, we demonstrated by EPR that MnIIis released from this site upon binding of the aminoglycoside antibiotic neomycin B (Kd=1.2 μM) to the hammerhead ribozyme. Neomycin B has previously been shown to inhibit the catalytic activity of this ribozyme (Uhlenbeck et al., Biochemistry1995, 34,11 186).