bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multiple‐start Monte Carlo docking method
Authors: Hart Trevor N. , Read Randy J. 
Published: May 2005

AbstractWe present a method to search for possible binding modes of molecular fragments at a specific site of a potential drug target of known structure. Our method is based on a Monte Carlo (MC) algorithm applied tothe translational and rotational degrees of freedom of the probe fragment. Starting from a randomly generated initial configuration, favorable bindingmodes are generated using a two‐step process. An MC run is first prformed in which the energy in the Metropolis algorithm is substituted by a score function that measures the average distance of the probe to the targetsurface. This has the effect of making buried probes move toward the targetsurface and also allows enhanced sampling of deep pockets. In a second MC run, a pairwise atom potential function is used, and the temperature parameter is slowly lowered during the run (Simulated Annealing). We repeat this procedure starting from a large number of different randomly generated initial configurations in order to find all energetically favourable docking modes in a specified region around the target. We test this method using two inhibitor‐receptor systems: Streptomyces griseus Proteinase B in complex with the third domain of the ovomucoid inhibitor from turkey, and dihydrofolate reductase from E. Coli in complex with methotrexate. The method could consistently reproduce the complex found in thecrystal structure searching from random initial positions in cubes ranging from 25 Å to 50 Å about the binding site. In the case of SGPB, we were also successful in docking to the native structure. In addition, we were successful in docking small probes in a search that included the entire protein surface. © 1992 Wiley‐Liss, Inc.
Common features of the conformations of antigen‐binding loops in immunoglobulins and application to modeling loop conformations
Authors: Tramontano Anna , Lesk Arthur M. 
Published: May 2005

AbstractUsing database screening techniques we have examined the relationship between antigen‐binding loops in immunoglobulins, and regions of similar conformation in other protein families. The conformations of most antigen‐binding loops are not unique to immunoglobulins. But in many cases, the geometrical relationship between the loop and the peptides flanking it differs between the immunoglobulins and other structures with the same loop. We assess model building by data base screening, compared with thatbased on canonical structures. © 1992 Wiley‐Liss, Inc.
Detection of native‐like models for amino acid sequences of unknown three‐dimensional structure in a data base of known protein conformations
Authors: Sippl Manfred J. , Weitckus Sabine 
Published: May 2005

AbstractWe present an approach which can be used to identify native‐like folds in a data base of protein conformations in the absence of any sequence homology to proteins in the data base. The method is based on a knowledge‐based force field derived from a set of known protein conformations. A given sequence is mounted on all conformations in the data base andthe associated energies are calculated. Using several conformations and sequences from the globin family we show that the native conformation is identified correctly. In fact the resolution of the force field is high enough to discriminate between a native fold and several closely related conformations. We then apply the procedure to several globins of known sequence but unknown three dimensional structure. The homology of these sequences to globins of known structures in the data base ranges from 49 to 17%. Withone exception we find that for all globin sequences one of the known globinfolds is identified as the most favorable conformation. These results are obtained using a force field derived from a data base devoid of globins of known structure. We briefly discuss useful applications in protein structurlresearch and future development of our approach. © 1992 Wiley‐Liss, Inc.
Pancreatic spasmolytic polypeptide: Crystallization, circular dichroism analysis, and preliminary X‐ray diffraction studies
Authors: Gajhede Michael , Thim Lars , Jørgensen Klavs H. , Melberg Steen G. 
Published: May 2005

AbstractPancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas has been crystallized by the hanging drop vapor diffusion method. Crystals suitable for X‐ray diffraction analysis were grown at pH 4.7 from a solution of 6% saturated ammonium sulfate. The space group is orthorhombic I222 or I212121 with unit cell parameters a = 54.38 Å, b = 72.29 Å, and c = 180.85 Å. There are three molecules of PSP per asymmetric unit and a water content of 46.9%. The crystals diffracts to an estimated resolution of 2.7 Å.The far‐UV CD spectrum of PSP shows some exceptional features which cannot be accounted for thoroughly in terms of standard secondary structures commonly seen in protein CD spectroscopy. With this limitation, the secondary structure analysis predicts 15% α‐helix, between 10 and 20% antiparallel β‐strand, 10% parallel β‐strand, 15% turn, and 25 to 40% of other structures. © 1992 Wiley‐Liss, Inc.
Modeling of substrate and inhibitor binding to phospholipase A2
Authors: Sessions Richard B. , Dauber‐Osguuthorpe Pnina , Campbell Malcolm M. , Osguthorpe David J. 
Published: May 2005

AbstractMolecular graphics and molecular mechanics techniques have been used to study the mode of ligand binding and mechanism of action of the enzyme phospholipase A2. A substrate–enzyme complex was constructed based on the crystal structure of the apoenzyme. The complex was minimized to relieve initial strain, and the structural and energetic features of the resultant complex analyzed in detail, at the molecular and residue level. The minimized complex was then used as a basis for examining the action of the enzyme on modified substrates, binding of inhibitors to the enzyme, and possible reaction intermedite complexes. The model is compatible with the suggested mechanism of hydrolysis and with experimental data about stereoselectivity, efficiency of hydrolysis of modified substrates, and inhibitor potency. In conclusion, the model can be used as a tool in evaluating new ligands as possible substrates and in the rational design of inhibitors, for the therapeutic treatment of diseases such as rheumatoid arthritis, atherosclerosis, and asthma. © 1992 Wiley‐Liss, Inc.
Variability of conformations at crystal contacts in BPTI represent true low‐energy structures: Correspondence among lattice packing and molecular dynamics structures
Authors: Kossiakoff Anthony A. , Randal Michael , Guenot Jeanmarie , Eignebrot Charles 
Published: May 2005

AbstractThe structure of five basic pancreatic trypsin inhibitor (BPTI) molecules are compared to establish the extent and nature of the conformational variability resulting from crystal packing effects. BPTI is an ideal system to evaluate such factors because of the availability of high resolution X‐ray models of five different BPTI structures, each in a different crystal packing environment. Differences observed among the structures are found to be distributed throughout the olecules, although the regions that display most variability are associated with the loop structures (residues 14–17 and 24–29). The regions of structure that show the largest rms deviations from the mean of the five packing motifs correlate well with the presence of intermolecular contacts in the crystal lattice. For most of the molecules there is also a correspondence between a larger number of intermolecular contacts and systematically higher B‐factors, although it is not appearent whether this is induced by the crystal contact or results from the fact that the contacts are made predominantly through surface loops. The conformational differences seen among the X‐ray models constitute more than local shifts at the lattice contact surfaces, and in fact involve in some cases the making and breaking of intramolecular H‐bonds. The magnitudes of the differences among packing models are significantly larger than those usually associated with changes induced by mutagenesis; for instance, the structural differences at the site of mutation observed on removing an internal disulfide from the molecule are significantly less than those associated with lattice contact effects. The crystal packing conformations are compared to representative structures of BPTI generated during a 96‐psec molecular dynamics (MD) simulation. This comparison shows a high level of correspondence between the protein flexibility indicated by the X‐ray and MD analyses, and specifically between those regions that are most variable. This suggests that the regions that show most variability among the crystal packing models are not artifacts of crystallization, but rather represent true low‐energy conformers that have been preferentially selected by crystallization factors. © 1992 Wiley‐Liss, Inc.
Multiple protein sequence alignment from tertiary structure comparison: Assignment of global and residue confidence levels
Authors: Russell Robert B. , Barton Geoffrey J. 
Published: May 2005

AbstractAn algorithm is presented for the accurate and rapid generation of multiple protein sequence alignments from tertiary structure comparisons. A preliminary multiple sequence alignment is performed using sequence information, which then determines an initial superposition of the structures. A structure comparison algorithm is applied to all pairs of proteins in the superimposed set and a similarity tree calculated. Multiple sequence alignments are then generated by following the tree from the branches to the root. At each branchpoint of the tree, a structure‐based sequence alignment and coordinate transformations are output, with the multiple alignment of all structures output at the root The algorithm encoded in STAMP (Structural Alignment of Multiple Proteins) is shown to give alignments in good agreement with published structural accounts within the dehydrogenase fold domains, globins, and serine proteinases.In order to reduce the need for visual verification, two similarity indices are introduced to determine the quality of each generated structural alignment. Sc quantifies the global structural similarity between pairs or groups of proteins, whereas Pij′ provides a normalized measure of the confidence in the alignment of each residue. STAMP alignments have the quality of each alignment characterized by Sc and Pij′ values and thus provide a reproducible resource for studies of residue conservation within structural motifs. © 1992 Wiley‐Liss, Inc.
Purification and crystallization of insecticidal δ‐endotoxin CryIIIB2 from Bacillus thuringiensis
Authors: Cody Vivian , Luft Joseph R. , Jensen Erik , Pangborn Walter , English Leigh 
Published: May 2005

AbstractCryIIIB2, an insecticidal protein from Bacillus thuringiensis has been crystallized from 0.6 M NaBr and HEPES buffer at pH 7.0 and X‐ray diffraction data collected on a native crystal to 2.4 Å. The insecticidal protein was obtained from a Bacillus thuringiensis (Bt) strain EG7231. Crystals of the endotoxin are orthorhombic, space group C2221, with unit cell dimensions of a = 122.44, b = and c = Å. A unit cell contains one molecule of the 67,000 Da endotoxin per asymmetric unit. © 1992 Wiley‐Liss, Inc.
Structural studies of the retroviral proteinase from avian myeloblastosis associated virus
Authors: Ohiendorf Douglas H. , Foundling Steven I. , Wendoloski John J. , Sedlacek Juraj , Strop Peter , Salemme F. Raymond 
Published: May 2005

AbstractThe structure of the retroviral proteinase from avian myeloblastosisassociated virus (MAV) has been determined and refined at 2.2 Å resolution. This structure is compared with those of homologous proteinases from Rous sarcoma virus (RSV) and human immunodeficiency type 1 virus (HIV). Through comparison with the structure of a proteinase‐inhibitor complex from HIV, a model of a complex between MAV proteinase and a peptide substrate has been generated. Examination of this model suggests structural basis for the diverse specifications of viral proteinases. © 1992 Wiley‐Liss, Inc.
What is the pitch of the α‐helical coiled coil?
Authors: Phillips George N. 
Published: May 2005

AbstractThe α‐helical, coiled‐coil protein motif is increasingly recognized in a variety of functional classes of proteins. The pitch of a coiled coil, or rate of winding of the α‐helices around each other, is a key determinant of both intra‐ and intermolecular interactions. Experimental measurements of the pitch of parallel two‐stranded coiled coils of muscle proteins, and examination of the recently determined structure of another two‐stranded coiled coil, the GCN4 transcription factor protein, suggest that the pitch has an average value of about 140 Å. This value is consistent with the observed number of residues per turn in α‐helices of globular proteins, the determinant of the inter‐helical packing within the coiled‐coil motif. An understanding of the structural determinants of this value for the pitch and possible variations will be important in defining the interactions of coiled‐coil proteins with other macromolecules. © 1992 Wiley‐Liss, Inc.
Crystal structures of two mutants of adenylate kinase from Escherichia coli that modify the Gly‐loop
Authors: Müller Christoph W. , Schulz Georg E. 
Published: May 2005

AbstractTwo mutants of adenylate kinase from Escherichia coli have been crystallized and analyzed by X‐ray diffraction at resolutions of 3.4 and 2.4 Å, respectively. These mutants are Pro‐9→Leu and Gly‐10→Val. They were selected for their positions in the highly conserved Gly‐loop forming a giant anion hole for the β‐phosphate of ATP (GTP) in adenylate kinases, H‐ras‐p21, and other nucleotide‐binding proteins. Mutants at these positions of H‐ras‐p21 cause cancer. In adenylate kinase these mutations cause smallish changes at the active site. Relating the structural changes to the known changes in catalysis indicates that these mutants hinder the induced‐fit movements. As a side result we find that mutant Pro‐9→Leu and wild‐type form one very similar crystal packing contact that is crystallographic in one case and noncrystallographic in the other, while all other packing contacts and the space groups are quite at variance. © 1993 Wiley‐Liss, Inc.
The role of local tight packing of hydrophobic groups in β‐structure
Authors: Vtyurin Nickolie 
Published: May 2005

AbstractAn analysis of the tendency of hydrophobic groups to tight packing on the surface of β‐sheets based on well‐known parameters of β‐sheets and hydrophobic groups was conducted. This analysis shows the existence of very limited numbers and clearly outlined architecture families of regular parts for the majority of β‐structure‐containing domains. Each family of architecture strongly depends on the number of β‐strands in the pure β‐domains and on the existence and number of additional α‐helixes and on the mutual arrangements β‐strands and α‐helixes along the chain in mixed α/β‐domains. This paper demonstrates that the tendency of hydrophobic groups to the local tight packing on the surface of β‐sheets is probably the main reason for the twist of β‐sheets. © 1993 Wiley‐Liss, Inc.
Crystallographic analysis of Thr‐200 → His human carbonic anhydrase II and its complex with the substrate, HCO
Authors: Xue Yafeng , Vidgren Jukka , Svensson L. Anders , Liljas Anders , Jonsson Bengt‐Harald , Lindskog Sven 
Published: May 2005

AbstractA complex of carbonic anhydrase (CA) with one of its substrates, bicarbonate, has been studied crystallographically. Human isoenzyme II was mutated at position 200 from threonine to histidine, which results in higher affinity for bicarbonate. The HCO ion binds in the active site to the zinc ion as a pseudo‐bidentate ligand which gives the metal a coordination geometry between tetrahedral and trigonal bipyramide. The water/hydroxide normally bound with tetrahedral coordination to the zinc is probably replaced by the OH group of the bicarbonate ion. The importance of residues Thr‐199 and Glu‐106 in controlling the binding orientation of HCO is discussed as well as the catalytic mechanism. Both the complex as well as the uncomplexed mutant were studied at 1.9 Å resolution. © 1993 Wiley‐Liss, Inc.
Preparation and initial characterization of crystals of the photoprotein aequorin from Aequorea victoria
Authors: Hannick Linda I. , Prasher Douglas C. , Schultz Leonard W. , Deschamps Jeffrey R. , Ward Keith B. 
Published: May 2005

AbstractCrystals of recombinant aequorin, the photoprotein from the jellyfish Aequorea victoria, have been grown from solutions containing sodium phosphate. The crystals grow as thin plates which diffract to beyond 2.2 Å resolution. The crystals are orthorhombic, space group P21212 1; the axes are a = 89.1(1), b = 88.4(1), and c = 52.7(1) Å. The asymmetric unit contains two molecules. Crystals exposed to calcium ion solutions emit a steady glow and slowly deteriorate, confirming that the crystals consist of a charged, competent photoprotein. This represents the first successful preparation of single crystals of a photoprotein suitable for diffraction analysis. © 1993 Wiley‐Liss, Inc.
Crystallization and preliminary crystallographic analysis of ribonuclease H from Thermus thermophilus HB8
Authors: Okumura Mika , Ishikawa Kohki , Kanaya Shigenori , Itaya Mitsuhiro , Morikawa Kosuke 
Published: May 2005

AbstractRibonuclease H from an extreme thermophile, Thermus thermophilus HB8, has been crystallized from solutions at low ionic strength. The crystals belong to the hexagonal space group P6 122 (or P6 522), with unit cell parameters a = b = 44.7 Å, c = 314.7 Å. They contain one 18,000 Mr molecule per asymmetric unit and diffract to 2.8 Å resolution. © 1993 Wiley‐Liss, Inc.
Identification of critical contact residues in the NC41 epitope of a subtype N9 influenza virus neuraminidase
Authors: Nuss Jacqueline M. , Whitaker Patricia Bossart , Air Gillian M. 
Published: May 2005

AbstractWe have examined amino acids on influenza virus neuraminidase (NA) subtype N9 (A/tern/Australia/G70c/75) which are in contact with monoclonal antibody NC41 to analyze individual interactions important for antibody recognition. The crystal structure of NA complexed with NC41 Fab1 shows antibody contacts at 19 amino acid residues on the NA surface which are localized on five polypeptide loops surrounding the enzyme active site. Fifteen mutant NA genes were constructed to encode a protein which contained a single amino acid substitution and these were tested for effects of the replacement on NC41 binding. Our data revealed that NAs with changes at 368, 400, and 434 completely lost NC41 recognition. NAs with side chains replaced at residues 346 and 373 exhibited binding reduced to less than 50% of wild‐type binding. Changes in seven other contacting residues, including substituted side chains which differed considerably from wild‐type NA in size and charge, had no significant effect on NC41 binding. These results indicate that only a few of the many residues which make up an epitope are crucial for interaction and provide the critical contacts required for antibody recognition. This implies that antibody escape mutants are selected only if they contain changes at these crucial sites, or changes which introduce bulky side chains that sterically prevent antibody attachment. © 1993 Wiley‐Liss, Inc.
Metal poison inhibition of carbonic anhydrase
Authors: Lindahl Martin , Svensson L. Anders , Liljas Anders 
Published: May 2005

AbstractCarbonic anhydrase is inhibited by the “metal poison” cyanide. Several spectroscopic investigations of carbonic anhydrase where the natural zinc ion has been replaced by cobalt have further strengthened the view that cyanide and cyanate bind directly to the metal. We have determined the structure of human carbonic anhydrase II inhibited by cyanide and cyanate, respectively, by X‐ray crystallography. It is shown that the inhibitors replace a molecule of water, which forms a hydrogen bond to the peptide nitrogen of Thr‐199 in the native structure. The coordination of the zinc ion is hereby left unaltered compared to the native crystal structure, so that the zinc coordinates three histidines and one molecule of water or hydroxyl ion in a tetrahedral fashion. The binding site of the two inhibitors is identical to what earlier has been suggested to be the position of the substrate (CO2) when attacked by the zinc bound hydroxyl ion. The peptide chain undergoes no significant alterations upon binding of either inhibitor. © 1993 Wiley‐Liss, Inc.
A geometrical constraint approach for reproducing the native backbone conformation of a protein
Authors: Saitoh Shin , Nakai Takahisa , Nishikawa Ken 
Published: May 2005

AbstractIt is known that the backbone conformation of a protein can be reproduced with precision once a correct contact map (two‐dimensional representation showing residue pairs in contact) is given as geometrical constraints. There is, however, no way to infer the correct contact map for a protein of unknown structure. We started with one‐dimensional constraints using the quantity N14 (the number of neighboring residues within the radius of 14 Å). Since the plot of N14 along a chain shows a good correlation with the corresponding amino acid sequence, the N14 profile obtained from the X‐ray structure is predictable from the sequence. Construction of backbone conformations under a given N14 profile was carried out in the following two steps: (1) a contact map from the N14 profile was produced by taking the product of N14 values of every two residues; (2) backbone conformations were generated by applying the distance geometry technique to distance constraints given by the contact map. If present, disulfide bonds in a protein, as well as the secondary structure, were treated as additional constraints, and both cases with or without the additional information were examined. The method was tested for 11 proteins of known structure, and the results indicated that the reproduced conformation was fairly good, using an X‐ray structure for comparison, for small proteins of less than 80 residues long. The basic assumption and effectiveness of the present method were compared with those of previous studies employing the geometrical constraint approach. It has become clear that the specific, one‐dimensional information (e.g., N14 profile) is more effective than nonspecific, two‐dimensional constraints, such as average interresidue distances between particular types of amino acids. © 1993 Wiley‐Liss, Inc.
Crystallization and preliminary X‐ray crystallographic analysis of arylesterase from Pseudomonas fluorescens
Authors: Kim Kyeong Kyu , Hwang Kwang Yeon , Choi Kang Duk , Kang Joo Hyun , Yoo Ook Joon , Suh Se Won 
Published: May 2005

AbstractLarge crystals of arylesterase from Pseudomonas fluorescens have been grown at room temperature using ammonium sulfate as a precipitant. They grow to dimensions of 0.7 × 0.7 × 0.6 mm3 within a month. The crystals belong to the trigonal space group P31 (or P32), with unit cell dimensions of a= 147.12 Å and c= 131.08 Å. The asymmetric unit seems to contain six molecules of dimeric aryles‐terase, with corresponding crystal volume per protein mass (VM) of 2.53 Å3/Da and solvent fraction of 51.5% by volume. The crystals diffract to at least 2.2 Å Bragg spacing when exposed to X‐rays from a rotating‐anode source. X‐ray data have been collected to 2.9 Å Bragg spacing from native crystals. © 1993 Wiley‐Liss, Inc.