bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical studies of relaxation of a monomeric subunit of HIV‐1 protease in water using molecular dynamics
Authors: Venable Richard M. , Carson Frederick W. , Brooks Bernard R. 
Published: May 2005

AbstractThe dynamic behavior of one 99‐residue subunit of the dimeric aspartyl protease of HIV‐1 was studied in a 160 psec molecular dynamics simulation at 300 K in water. The crystal structure of one of the identical subunits of the dimer was the starting point, with the aqueous phase modeled by 4,331 explicit waters in a restrained spherical droplet Analysis of the simulations showed that the monomer displayed considerable flexibility in the interfacial portions of the flap (the region which folds over the substrate), the N‐ and C‐0termini, and, to a lesser extent, the active site. The flap undergoes significant motion as an independent rigid finger, but without the cantilever previously reported hi a simulation of the dimer. The N‐terminus displayed the greatest fluctuational disorder whereas the C‐terminus exhibited the greatest root mean square movement from the crystal structure. The central core of the monomer had a heavy‐atom root mean square deviation from the initial structure of about 3.0 Å during the latter half of the simulation. Although this is larger than the 1.6 Å found for comparable simulations of typical globular proteins, the general features of the tertiary structure were preserved over the course of the simulation. Overall, these results indicate that the relaxed structure obtained in these simulations may provide a better model for the tertiary structure of the solvated HIV‐1 protease monomer than the subunit conformation seen in the X‐ray crystallographic structure of the dimer. Except in the flap region, the design of compounds intended to interfere with dimerization should take this relaxation and the flexibility of the solvated monomer, especially at the termini, into account. © 1993 Wiley‐Liss, Inc.
Computer simulation of antibody binding specificity
Authors: Pellegrini Matteo , Doniach Sebastian 
Published: May 2005

AbstractA Monte Carlo algorithm that searches for the optimal docking configuration of hen egg white lysozyme to an antibody is developed. Both the lysozyme and the antibody are kept rigid. Unlike the work of other authors, our algorithm does not attempt to explicitly maximize surface contact, but minimizes the energy computed using coarse‐grained pair potentials. The final refinement of our best solutions using all‐atom OPLS potentials (Jorgensen and Tirado‐Rives8) consistently yields the native conformation as the preferred solution for three different antibodies. We find that the use of an exponential distance‐dependent dielectric function is an improvement over the more commonly used linear form. © 1993 Wiley‐Liss, Inc.
Recombinant antineuraminidase single chain antibody: Expression, characterization, and crystallization in complex with antigen
Authors: Malby Robyn L. , Caldwell J. Bruce , Gruen L. Clem , Harley Vincent R. , Ivancic Neva , Kortt Alexander A. , Lilley Glenn G. , Power Barbara E. , Webster Robert G. , Colman Peter M. , Hudson Peter J. 
Published: May 2005

AbstractThe variable heavy (VH) and variable light (VL) genes of NC10, a monoclonal antibody with specificity toward N9 neuraminidase (NA), were cloned and sequenced. A single chain Fv (scFv) fragment of NC10, consisting of VH and VL domains joined by a peptide linker, was designed, constructed and expressed in the E. coli expression vector pPOW. The N‐terminal secretion signal PelB directed the synthesized protein into the periplasm where it was associated with the insoluble membrane fraction. An octapeptide (FLAG) tail was fused to the C‐terminus of the single chain Fv to aid in its detection and remained intact throughout the protein purification process. NC10 scFv was purified by solubilization of the E. coli membrane fraction with guanidinium hydrochloride followed by column chromatography. The purified NC10 scFv showed binding affinity for its antigen, NA, 2‐fold lower than that of the parent Fab. The complex between NA and the scFv has been crystallized by the vapor diffusion method. The crystals are tetragonal, space group P4212, with unit cell dimensions a = b = 141 Å, c = 218 Å. © 1993 Wiley‐Liss, Inc.
Surface motifs by a computer vision technique: Searches, detection, and implications for protein–ligand recognition
Authors: Fischer Daniel , Norel Raquel , Wolfson Haim , Nussinov Ruth 
Published: May 2005

AbstractWe describe the application of a method geared toward structural and surface comparison of proteins. The method is based on the Geometric Hashing Paradigm adapted from Computer Vision. It allows for comparison of any two sets of 3‐D coordinates, such as protein backbones, protein core or protein surface motifs, and small molecules such as drugs. Here we apply our method to 4 types of comparisons between pairs of molecules: (1) comparison of the backbones of two protein domains; (2) search for a predefined 3‐D Cαmotif within the full backbone of a domain; and in particular, (3) comparison of the surfaces of two receptor proteins; and (4) comparison of the surface of a receptor to the surface of a ligand. These aspects complement each other and can contribute toward a better understandingof protein structure and biomolecular recognition. Searches for 3‐D surface motifs can be carried out on either receptors or on ligands. The latter may result in the detection of pharmacophoric patterns. If the surfaces of the binding sites of either the receptors or of the ligands are relatively similar, surface superpositioning may aid significantly in the docking problem. Currently, only distance invariants are used in the matching, although additional geometric surface invariants are considered. The speed of our Geometric Hashing algorithm is encouraging, with a typical surface comparison taking only seconds or minutes of CPU time on a SUN 4 SPARC workstation. The direct application of this method to the docking problem is also discussed. We demonstrate the success of this methodin its application to two members of the globin family and to two dehydrogenases. © 1993 Wiley‐Liss, Inc.
Automated docking in crystallography: Analysis of the substrates of aconitase
Authors: Goodsell David S. , Lauble Hans , Stout C. David , Olson Arthur J. 
Published: May 2005

AbstractAutomated docking of substrates to proteins of known structure aids the process of crystallographic analysis in two ways. First, automated docking can be used to generate a small number of starting models for substrates using only protein coordinates from an early stage of refinement. Second, automated docking provides a method for exploring aspects of catalysis that are inaccessible to crystallography by postulating binding modes of catalytic intermediates. This paper describes the use of automated docking to explore the binding of substrates to aconitase. The technique starts with a substrate molecule in an arbitrary configuration and position and finds favorable docked configrations in a (static) protein active site based on a molecular mechanics type force field. Using protein coordinates from an early stage of refinement of an aconitase‐isocitrate complex, we successfully predicted the binding configuration of isocitrate. Four configurations were found, the energetically most favorable of which fit the observed electron density well and was used as a starting model for further refinement. Two configurations were found in citrate docking experiments, the second of which approximates the mode of substrate binding in an aconitasenitrocitrate complex. We were also able to propose two binding modes of the catalytic intermediate cis‐aconitate. These correspond closely to the isocitrate and the citrate binding modes. The relation of these new results to the proposed reaction mechanism is discussed. © 1993 Wiley‐Liss, Inc.
Performance evaluation of amino acid substitution matrices
Authors: Henikoff Steven , Henikoff Jorja G. 
Published: May 2005

AbstractSeveral choices of amino acid substitution matrices are currently available for searching and alignment applications. These choices were evaluated using the BLAST searching program, which is extremely sensitive to differences among matrices, and the Prosite catalog, which lists members of hundreds of protein families. Matrices derived directly from either sequence‐based or structurebased alignments of distantly related proteins performed much better overall than extrapolated matrices based on the Dayhoff evolutionary model. Similar results were obtained with the FASTA searching program. Improved performance appears to be general rather than family‐specific, reflecting improved accuracy in scoring alignments. An implementation of a multiple matrix strategy was also tested. While no combination of three matrices performed as well as the single best matrix, BLOSUM 62, good results were obtained using a combination of sequence‐based and structure‐based matrices. This hybrid set of matrices is likely to be useful in certain situations. Our results illustrate the importance of matrix selection and value of a comprehensive approach to evaluation of protein comparison tools. © 1993 Wiley‐Liss, Inc.
Primary structure effects on peptide group hydrogen exchange
Authors: Bai Yawen , Milne John S. , Mayne Leland , Englander S. Walter 
Published: May 2005

AbstractThe rate of exchange of peptide group NH hydrogens with the hydrogens of aqueous solvent is sensitive to neighboring side chains. To evaluate the effects of protein side chains, all 20 naturally occurring amino acids were studied using dipeptide models. Both inductive and steric blocking effects are apparent. The additivity of nearest‐neighbor blocking and inductive effects was tested in oligo‐and polypeptides and, suprisingly, confirmed. Reference rates for alanine‐containing peptides were determined and effects of temperature considered. These results provide the information necessary to evaluate measured protein NH to ND exchange rates by comparing them with rates to be expected for the same amino acid sequence is unstructured aligo‐ and polypeptides. The application of this approach to protein studies is discussed. © 1993 Wiley‐Liss, Inc.
Isotope effects in peptide group hydrogen exchange
Authors: Connelly Gregory P. , Bai Yawen , Jeng Mei‐Fen , Englander S. Walter 
Published: May 2005

AbstractKinetic and equilibrium isotope effects in peptide group hydrogen exchange reactions were evaluated. Unlike many other reactions, Kinetic isotope effects in amide hydrogen exchange are small because exchange pathways are not limited by bondbreaking steps. Rate constants for the acid‐cat‐alyzed exchange of peptide group NH, ND, and NT in H2O are essentially identical, but a solvent esotope effect doubles the rate in D2O. Rate constants for base‐catalyzed exchange in H2O decrease slowly in the order NH > ND > NT. The alkaline rate constant in D2O is very close to that in H2O when account is taken of the glass electrode pH artifact and the difference in solvent ionization constant. Small equilibrium isotope effects lead to an excess equilibrium accumulation of the heavier isotopes by the peptide group. Results obtained are expressed in terms of rate constants for the random coil polypeptide, poly‐DL‐alanine, to provide reference rates for protein hydrogen exchange studies as described in Bai et al. [preceding paper in this issue]. © 1993 Wiley‐Liss, Inc.
Molecular basis of cooperativity in protein folding IV. Core: A general cooperative folding model
Authors: Freire Ernesto , Haynie Donald T. , Xie Dong 
Published: May 2005

AbstractThe cooperative nature of the protein folding process is independent of the characteristic fold and the specific secondary structure attributes of a globular protein. A general folding/unfolding model should, therefore, be based upon structural features that transcend the peculiarities of α‐helices, β‐sheets, and other structural motifs found in proteins. The studies presented in this paper suggest that a single structural characteristic common to all globular proteins is essential for cooperative folding. The formation of a partly folded state from the native state results in the exposure to solvent of two distinct regions: (1) the portions of the protein that are unfolded; and (2) the “complementary surfaces,” located in the regions of the protein that remain folded. The cooperative character of the folding/unfolding transition is determined largely by the energetics of exposing complementary surface regions to the solvent. By definition, complementary regions are present only in partly folded states; they are absent from the native and unfolded states. An unfavorable free energy lowers the probability of partly folded states and increases the cooperativity of the transition. In this paper we present a mathematical formulation of this behavior and develop a general cooperative folding/unfolding model, termed the “complementary region” (CORE) model. This model successfully reproduces the main properties of folding/unfolding transitions without limiting the number of partly folded states accessible to the protein, thereby permitting a systematic examination of the structural and solvent conditions under which intermediates become populated. It is shown that the CORE model predicts two‐state folding/unfolding behavior, even though the two‐state character is not assumed in the model. © 1993 Wiley‐Liss, Inc.
Solution structure of tertiapin determined using nuclear magnetic resonance and distance geometry
Authors: Xu Xiaobing , Nelson Jeffrey W. 
Published: May 2005

AbstractThe solution structure of tertiapin, a 21‐residue bee venom peptide, has been characterized by circular dichroism (CD), two‐dimensional nuclear magnetic resonance (NMR) spectroscopy, and distance geometry. A total of 21 lowest error structures were obtained from distance geometry calculations. Superimposition of these structures shows that the backbone of tertiapin is very well defined. One type‐I reverse turn from residue 4 to 7 and an α‐helix from residue 12 to 19 exist in the structure of tertiapin. The α‐helical region is best defined from both conformational analysis and structural superimposition. The overall three‐dimensional structure of tertiapin is highly compact resulting from side chain interactions. The structural information obtained from CD and NMR are compared for both tertiapin and apamin (ref. 3), another bee venom peptide. Tertiapin and apamin have some similar secondary structure, but display different tertiary structures. © 1993 Wiley‐Liss, Inc.
Orientational sampling and rigid‐body minimization in molecular docking
Authors: Meng Elaine C. , Gschwend Daniel A. , Blaney Jeffrey M. , Kuntz Irwin D. 
Published: May 2005

AbstractThe biological activities of proteins depends on specific molecular recognition and binding. Computational methods for predicting binding modes can facilitate the discovery and design of ligands and yeild information on the factors governing complementarity. The DOCK suite of programs has been applied to several systems; here, the degree of orientational sampling required to reproduce and identify known binding modes, with and without rigid‐body energy minimization, is investigated for four complexes. There is a tradeoff between sampling and minimization. The known binding modes can be identified with intensive sampling alone (10,000 to 20,000 orientations generated per system) or with moderate sampling combined with minimization. Optimization improves energies significantly, particularly when steric clashes are present, and brings many orientations closer to the experimentally observed position. Whether or not minimization is performed, however, sampling must be sufficient to find at least one structure in the vicinity of the presumed true binding mode. Hybrid approaches combining docking and minimization are promising and will become more viable with the use of faster algorithms and the judicious selection of fewer orientations for minimization. © 1993 Wiley‐Liss, Inc.
Crystallization and prelilminary X‐ray investigation of barster, the intracellular inhibitor of barnase
Authors: Guillet Valérie , Lapthorn Adrian , Fourniat Jacky , Benoit Jean‐Pierre , Hartley Robert W. , Mauguen Yves 
Published: May 2005

AbstractCrystals of barstar, the intracellular inhibitor of the extracellular ribonuclease produced by Bacillus amyloliquefaciens (barnase), were obtained through vapor phase equilibration using the hanging drop technique. Three crystal forms have been characterized. Forms I and II, crystallized eithr in potetragonal; they exhibit a superstructure along the c‐axis. Form III crystals, suitable for a high resolution structure determination, were grown from 55‐65% ammomnium sulfate. This crystal form is hexagonal and diffracts to at least 2 Å resolution at a synchrotron radiation source. It belongs to the hexagonal space group P6, with unit cell dimensions a = b = 143.6 Å, c = 35.6 Å. There are four molecules of barstar in the asymmetric unit. X‐ray data have been collected to 2.2 Å Bragg sapcing. The structure determination is underway in order to analyze conformational changes of barstar upon complexation with barnas. © 1993 Wiley‐Liss, Inc.
Crystal structure of Escherichia coli RNase HI in complex with Mg2+ at 2.8 Å resolution: Proof for a single Mg2+‐binding site
Authors: Katayanagi Katsuo , Okumura Mika , Morikawa Kosuke 
Published: May 2005

AbstractTo obtain more precise insight into the Mg2+‐binding site essential for RNase HI catalytic activity, we have determined the crystal structure of E. coli RNase HI in complex with Mg2+. The analyzed cocrystal, which is not isomorphous with the Mg2+‐free crystal previously refined at 1.48 Å resolution, was grown at a high MgSO4 concentration more than 100 mM so that even weakly bound Mg2+ sites could be identified. The structure was solved by the molecular replacement method, using the Mg2+‐free crystal structure as a search model, and was refined to give a final R‐value of 0.190 for intensity data from 10 to 2.8 Å, using the XPLOR and PROLSQ programs. The backbone structures are in their entirety very similar to each other between the Mg2+‐bound and the metal‐free crystals, except for minor regions in the enzyme interface with the DNA/RNA hybrid. The active center clearly revealed a single Mg2+ atom located at a position almost identical to that previously found by the soaking method. Although the two metal‐ion mechanism had been suggested by another group (Yang, W., Hendrickson, W.A., Crouch, R.J., Satow, Y. Science 249:1398‐1405, 1990) and partially supported by the crystallographic study of inactive HIV‐1 RT RNase H fragment (Davies, J.F., II, Hostomska, Z., Hostomsky, Z., Jordan, S.R., Matthews, D. Science 252:88‐95, 1991), the present result excludes the possibility that RNase HI requires two metal‐binding sites for activity. In contrast to the features in the metal‐free enzyme, the side chains of Asn‐44 and Glu‐48 are found to form coordinate bonds with Mg2+ in the metal‐bound crystal. © 1993 Wiley‐Liss, Inc.
Hundreds of ankyrin‐like repeats in functionally diverse proteins: Mobile modules that cross phyla horizontally?
Authors: Bork Peer 
Published: May 2005

AbstractBased on pattern searches and systematic database screening, almost 650 different ankyrin‐like (ANK) repeats from nearly all phyla have been identified; more than 150 of them are reported here for the first time. Their presence in functionally diverse proteins such as enzymes, toxins, and transcription factors strongly suggests domain shuffling, but their occurrence in prokaryotes and yeast excludes exon shuffling. The spreading mechanism remains unknown, but in at least three cases horizontal gene transfer appears to be involved. ANK repeats occur in at least four consecutive copies. The terminal repeats are more variable in sequence. One feature of the internal repeats is a predicted central hydrophobic α‐helix, which is likely to interact with other repeats. The functions of the ankyrin‐like repeats are compatible with a role in protein‐protein interactions. © 1993 Wiley‐Liss, Inc.
A method to recognize distant repeats in protein sequences
Authors: Heringa Jaap , Argos Patrick 
Published: May 2005

AbstractAn automated algorithm is presented that delineates protein sequence fragments which display similarity. The method incorporates a selection of a number of local nonoverlapping sequence alignments with the highest similarity scores and a graphtheoretical approach to elucidate the consistent start and end points of the fragments comprising one or more ensembles of related subsequences. The procedure allows the simultaneous identification of different types of repeats within one sequence. A multiple alignment of the resulting fragments is performed and a consensus sequence derived from the ensemble(s). Finally, a profile is constructed form the multiple alignment to detect possible and more distant members within the sequence. The method tolerates mutations in the repeats as well as insertions and deletions. The sequence spans between the various repeats or repeat clusters may be of different lengths. The technique has been applied to a number of proteins where the repeating fragments have been derived from information additional to the protein sequences. © 1993 Wiley‐Liss, Inc.
Essential dynamics of proteins
Authors: Amadei Andrea , Linssen Antonius B. M. , Berendsen Herman J. C. 
Published: May 2005

AbstractAnalysis of extended molecular dynamics (MD) simulations of lysozyme in vacuo and in aqueous solution reveals that it is possible to separate the configurational space into two subspaces: (1) an “essential” subspace containing only a few degrees of freedom in which anharmonic motion occurs that comprises most of the positional fluctuations; and (2) the remaining space in which the motion has a narrow Gaussian distribution and which can be considered as “physically constrained.” If overall translation and rotation are eliminated, the two spaces can be constructed by a simple linear transformation in Cartesian coordinate space, which remains valid over several hundred picoseconds. The transformation follows from the covariance matrix of the positional deviations. The essential degrees of freedom seem to describe motions which are relevant for the function of the protein, while the physically constrained subspace merely describes irrelevant local fluctuations. The near‐constraint behavior of the latter subspace allows the separation of equations of motion and promises the possibility of investigating independently the essential space and performing dynamic simulations only in this reduced space. © 1993 Wiley‐Liss, Inc.