bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fuzzy cluster analysis of molecular dynamics trajectories
Authors: Gordon Heather L. , Somorjai Rajmund L. 
Published: May 2005

AbstractWe propose fuzzy clustering as a method to analyze molecular dynamics (MD) trajectories, especially of proteins and polypeptides. A fuzzy cluster analysis locates classes of similar three‐dimensional conformations explored during a molecular dynamics simulation. The method can be readily applied to results from both equilibrium and nonequilibrium simulations, with clustering on either global or local structural parameters. The potential of this technique is illustrated by results from fuzzy cluster analyses of trajectories from MD simulations of various fragments of human parathyroid hormone (PTH). For large molecules, it is more efficient to analyze the clustering of root‐mean‐square distances between conformations comprising the trajectory. We found that the results of the clustering analysis were unambiguous, in terms of the optimal number of clusters of conformations, for the majority of the trajectories examined. The conformation closest to the cluster center can be chosen as being representative of the class of structures making up the cluster, and can be further analyzed, for example, in terms of its secondary structure. The CPU time used by the cluster analysis was negligible compared to the MD simulation time. © 1992 Wiley‐Liss, Inc.
A model of the platelet factor 4 complex with heparin
Authors: Stuckey Jeanne A. , Charles Robert St. , Edwards Brian F. P. 
Published: May 2005

AbstractA model of heparin bound to bovine platelet factor 4 (BPF4) was completed using a graphically designed heparin molecule and the crystallographic coordinates of the native bovine platelet factor 4 tetramer. The oligosaccharides had a chain length of at least eight disaccharide units with the major repeating disaccharide unit consisting of (I→4)‐O‐(α‐L‐idopyranosyluronic acid 2‐sulfate)‐(l→4)‐(2‐deoxy‐2‐sulfamino‐2‐D‐glucopyra‐nosyl 6‐sulfate). Each disaccharide unit carried a −4.0 charge. The structure of BPF4 was solved to 2.6 Å resolution with R = 0.237. Each monomer of BPF4 contains an α‐helix lying across 3 strands of antiparallel β‐sheet. Each helix has four lysines, which have been implicated in heparin binding. These lysine residues are predominantly on one side of the helix and are solvent accessible. Electrostatic calculations performed on the BPF4 tetramer show a ring of strong, positive charge which runs perpendicularly across the helices. Included in this ring of density is His‐38, which has been shown by NMR to have a large pKa shift when heparin binds to BPF4. Our model of heparin bound to PF4 has the anionic polysaccharide perpendicular to the α‐helices, wrapped about the tetramer along the ring of positive charge, and salt linked to all four lysines on the helix of each monomer. © 1992 Wiley‐Liss, Inc.
Regulation of oxygen affinity by quaternary enhancement: Does hemoglobin ypsilanti represent an allosteric intermediate?
Authors: Doyle Michael L. , Lew George , Turner George J. , Rucknagel Donald , Ackers Gary K. 
Published: May 2005

AbstractRecent crystallographic studies on the mutant human hemoglobin Ypsilanti (β99 Asp→xsTyr) have revealed a previously unknownquaternary structure called “quaternary Y” and suggested that the new structure may represent an important intermediate in the cooperative oxygenationpathway of normal hemoglobin.15 Here we measure the oxygenation and subunit assembly properties of hemoglobin Ypsilanti and five additionalβ99 mutants (Asp β99→Val, Gly, Asn, Ala, His) totest for consistency between their energetics and those of the intermediatespecies of normal hemoglobin.Overall regulation of oxygen affinity in hemoglobin Ypsilanti is found to originate entirely from 2.6 kcal of quaternary enhancement, such that thetetramer oxygenation affinity is 85‐fold higher than for binding to the dissociated dimers. Equal partitioning of this regulatory energy among the four tetrameric binding steps (0.65 kcal per oxygen) leads toa noncooperative isotherm with extremely high affinity (pmedian = .14 torr). Temperature and pH studies of dimer‐tetramer assembly and sulfhydryl reaction kinetics suggest that oxygenation‐dependent structural changes in hemoglobin Ypsilanti are small. These properties are quite different from the recently characterized allosteric intermediate, which has two ligands bound on the same side of the α1β2 interface (see ref. 1 for review). The combined results do, however, support the view that quaternary Y may represent the intermediate cooperativity state of normal hemoglobin that binds the last oxygen. © 1992 Wiley‐Liss, Inc.
Crystal structure of human immunoglobulin fragment Fab new refined at 2.0 Å esolution
Authors: Saul Frederick A. , Poljak Roberto J. 
Published: May 2005

AbstractThe three‐dimensional structure of the human immunoglobulin fragment Fab New (IgG1,λ) has been refined to a crystal‐lographic R‐factor of 16.9% to 2Å resolution. Rms deviations of the final model from ideal geometry are 0.014 Å for bond distances and 3.03° for bond angles. Refinement was based on a new X‐ray data set including 28,301 reflections with F>2.5σ(F) from 6.0 to 2.0 Å resolution. The starting model for the refinement procedure reported here is from the Brookhaven Protein Data Bank entry 3FAB (rev. 1981). Differences between the initial and final models include modified polypeptide‐chain folding in the third complementarity‐determining region (CDR3) and the third framework region (FR3) of VH and in some exposed loops of CL and CHl. Amino acid sequencechanges were determined at a number of positions by inspection of difference electron density maps. The incorporation of amino acid sequence changes results inan improved VH framework model for the “humanization” of monoclonal antibodies.
Folding protein α‐carbon chains into compact forms by monte carlo methods
Authors: Covell David G. 
Published: May 2005

AbstractA method is presented for generating folded chains of specific aminoacid sequences on a simple cubic lattice. Monte Carlo simulations are used to transform extended geometries of simplified α‐carbon chainsfor eight small monomeric globular proteins into folded states. Permitted chain transitions are limited to a few types of moves, all restricted to occur on the lattice. Crude residue–residue potentials derived from statistical structure data are used to describe the energies for each conformer. The low resolution structures obtained by this procedure contain many of the correct gross features of the native folded architectures with respect to average residue energy per nonbonded contact, segment density, and location of surface loops and disulfide pairs. Rms deviations between these and the native X‐ray structures and percentage of native long‐range contacts found in these final folded structures are 7.6 ± 0.7 Å and 48 ± 3%, respectively. This procedure can be useful for predicting approximate tertiary interactions from amino acid sequence. © 1992 Wiley‐Liss, Inc.
Generation of a substructure library for the description and classification of protein secondary structure. I. Overview of the methods and results
Authors: Prestrelski Steven J. , Williams Arthur L. , Liebman Michael N. 
Published: May 2005

AbstractProtein secondary structure has been typically classified into four major classes—α‐helices, extended strands, reverse turns, and loops. Available methods for secondary structure analysis utilize predefined structure templates to search for structural matches among proteins. By this approach a significant portion of a proteins backbone conformation is assigned to one of a limited number of conformations or, if unassigned, to random coil. To expand our ability to describe protein secondary structure, we have developed an algorithm that operates independently of a predefined structure template. The procedure uses two geometric descriptors, the linear distance and the backbone dihedral angle, to represent the conformation form the α‐carbon coordinates. The algorithm functions by searching for conformationally equivalent, contiguous fragments without regard to secondary structural classification and is thus independent of the complexity of the backbone fold. The result is a library of conformationally equivalent structure fragments that exhibit some novel characteristics. The library contains features that reproduce the major secondary structure classes as well as defining conformations previously described only as random or undefined conformations. Additionally, the library defines several subclassifications of β‐strands. We present here a validation of this method and a presentation and discussion of the most significant results. In a second study, we report the results of application of this method to spectra‐structure correlations in Fourier transform infrared spectroscopy. © 1992 Wiley‐Liss, Inc.
MD simulation of subtilisin BPN′ in a crystal environment
Authors: Heiner Andreas P. , Berendsen Herman J. C. , van Gunsteren Wilfred F. 
Published: May 2005

AbstractIn this paper we present a molecular dynamics (MD) simulation of subtilisin BPN′ in a crystalline environment containing four protein molecules and solvent. Con‐formational and dynamic properties of the molecules are compared with each other and with respect to the X‐ray structure to test the validity of the force field. The agreement between simulated and experimental structure using the GROMOS force field is better than that obtained in the literature using other force fields for protein crystals. The overall shape of the molecule is well preserved, as is the conformation of α‐helices and β‐strands. Structural differences are mainly found in loop regions. Solvent networks found in the X‐ray structure were reproduced by the simulation, which was unbiased with respect to the crystalline hydration structure. These networks seem to play an important role in the stability of the protein; evidence of this is found in the structure of the active site. The weak ion binding site in the X‐ray structure of subtilisin BPN′ is occupied by a monovalent ion. When a calcium ion is placed in the initial structure, three peptide ligands are replaced by 5 water ligands, whereas a potassium ion retains (in part) its original ligands. Existing force fields yield a reliable method to probe local structure and short‐time dynamics of proteins, providing an accuracy of about 0.1 nm. © 1992 Wiley‐Liss, Inc.
Application of a directed conformational search for generating 3‐D coordinates for protein structures from α‐carbon coordinates
Authors: Bassolino‐Klimas Donna , Bruccoleri Robert E. 
Published: May 2005

AbstractA directed conformational search algorithm using the program CONGEN (ref. 3), which samples backbone conformers, is described. The search technique uses information from the partially built structures to direct the search process and is tested on the problem of generating a full set of backbone Cartesian coordinates given only α‐carbon coordinates. The method has been tested on six proteins of known structure, varying in size and classification, and was able to generate the original backbone coordinates with RMSs ranging from 0.30–0.87Å for the α‐carbons and 0.5–0.99Å RMSs for the backbone atoms. Cis peptide linkages were also correctly identified. The procedure was also applied to two proteins available with only α‐carbon coordinates in the Brookhaven Protein Data Bank; thioredoxin (SRX) and triacyiglycerol acylhydrolase (TGL). All‐atom models are proposed for the backbone of both these proteins. In addition, the technique was applied to randomized coordinates of flavodoxin to assess the effects of irregularities in the data on the final RMS. This study represents the first time a deterministic conformational search was used on such a large scale. © 1992 Wiley‐Liss, Inc.
Investigation of the function of mutated cellulose‐binding domains of Trichoderma reesei cellobiohydrolase I
Authors: Reinikainen Tapani , Ruohonen Laura , Nevanen Tarja , Laaksonen Leif , Kraulis Per , Jones T. Alwyn , Knowles Jonathan K. C. , Teeri Tuula T. 
Published: May 2005

AbstractThe function of the cellulosebinding domain (CBD) of the cellobiohydrolase I of Trichoderma reesei was studied by site‐directed mutagenesis of two amino acid residues identified by analyzing the 3D structure of this domain. The mutant enzymes were produced in yeast and tested for binding and activity on crystalline cellulose. Mutagenesis of the tyrosine residue (Y492) located at the tip of the wedge‐shaped domain to alanine or aspartate reduced the binding and activity on crystalline cellulose to the level of the core protein lacking the CBD. However, there was no effect on the activity toward small oligosaccharide (4‐methylumbellifery1 β‐D‐lactoside). The mutation tyrosine to histidine (Y492H) lowered but did not destroy the cellulose binding, suggesting that the interaction of the pyranose ring of the substrate with an aromatic side chain is important. However, the catalytic activity of this mutant on crystalline cellulose was identical to the other two mutants. The mutation P477R on the edge of the other face of the domain reduces both binding and activity of CBHI. These results support the hypothesis that both surfaces of the CBD are involved in the interaction of the binding domain with crystalline cellulose. © 1992 Wiley‐Liss, Inc.
Modeling the anti‐CEA antibody combining site by homology and conformational search
Authors: Mas Maria T. , Smith Kenneth C. , Yarmush David L. , Aisaka Kazuo , Fine Richard M. 
Published: May 2005

AbstractA model for an antibody specific for the carcinoembryonic antigen (CEA) has been constructed using a method which combines the concept of canonical structure with conformational search. A conformational search technique is introduced which couples random generation of backbone loop conformations to a simulated annealing method for assigning side chain conformations. This technique was used both to verify conformations selected from the set of known canonical structures and to explore conformations available at the H3 loop in CEA ab initio. Canonical structures are not available for H3 due to its variability in length, sequence, and observed conformation in known antibody structures Analysis of the results of conformational search resulted in three equally probable conformations for H3 loop in CEA. Force field energies, solvation free energies, exposure of charged residues and burial of hydrophobic residues, and packing of hydrophobic residues at the base of the loop were used as selection criteria. The existence of three equally plausible structures may reflect the high degree of flexibility expected for an exposed loop of this length. The nature of the combining site and features which could be important to interaction with antigen are discussed. © 1992 Wiley‐Liss, Inc.
Identification of novel peptide antagonists for GPIIb/IIIa from a conformationally constrained phage peptide library
Authors: O'Neil Karyn T. , Hoess Ronald H. , Jackson Sharon A. , Ramachandran Narayana Swamy , Mousa Shaker A. , DeGrado William F. 
Published: May 2005

AbstractMethods have recently been developed to present vast libraries of random peptides on the surface of filamentous phage. To introduce a degree of conformational constraint into random peptides, a library of hexapeptides flanked by cysteine residues (capable of forming cyclic disulfides) was constructed. This library was screened using the platelet glycoprotein, IIb/IIIa, which mediates the aggregation of platelets through binding of fibrinogen. A variety of peptides containing the sequence Arg‐Gly‐Asp or Lys‐Gly‐Asp were discovered and synthesized. The cyclic, disulfide bonded forms of the peptides bound IIb/IIIa with dissociation constants in the nanomolar range, while reduced forms or an analogue in which Ser replaced the Cys residues bound considerably less tightly. These results demonstrate the feasibility for introducing conformational constraints into random peptide libraries and also demonstrates the potential for using phage peptide libraries to discover pharmacologically active lead compounds. © 1992 Wiley‐Liss, Inc.
Insertion of peptide chains into lipid membranes: An off‐lattice Monte Carlo dynamics model
Authors: Milik Mariusz , Skolnick Jeffrey 
Published: May 2005

AbstractA combination of dynamic Monte Carlo simulation techniques with a hydropathy scale method for the prediction of the location of transmembrane fragments in membrane proteins is described. The new hydropathy scale proposed here is based on experimental data for the interactions of tripeptides with phospholipid membranes (Jacobs, R.E., White, S.H. Biochemistry 26:6127–6134, 1987) and the self‐solvation effect in protein systems (Roseman, M.A., J. Mol. Biol. 200:513–522, 1988). The simulations give good predictions both for the state of association and the orientation of the peptide relative to the membrane surface of a number of peptides including Magainin2, M2δ, and melittin. Furthermore, for Pf1 bacterio‐phage coat protein, in accord with experiment, the simulations predict that the C‐terminus forms a transmembrane helix and the N‐terminus forms a helix which is adsorbed on the surface of the bilayer. Finally, the present series of simulations provide a number of insights into the mechanism of insertion of peptides into cell membranes. © 1993 Wiley‐Liss, Inc.
Characterization of proline‐containing α‐helix (helix F model of bacteriorhodopsin) by molecular dynamics studies
Authors: Sankararamakrishnan R. , Vishveshwara Saraswathi 
Published: May 2005

AbstractMany of the bilayer spanning segments of membrane transport proteins contain proline residues, and most of them are believed to occur in α‐helical form. A proline residue in the middle of an α‐helix is known to produce a bend in the helix, and recent studies have focused on characterizing such a bend at atomic level. In the present case, molecular dynamics (MD) studies are carried out on helix F model of bacteriorhodopsin (BR) Ace‐(Ala)7‐Trp‐(Ala)2‐Tyr‐Pro‐(Ala)2‐Trp‐(Ala)8‐NHMe and compared with Ace‐(Ala)7‐Trp‐(Ala)2‐Tyr‐(Ala)3‐Trp‐(Ala)8‐NHMe in which the proline is replaced by alanine. The bend in the helix is characterized by structural parameters such as kink angle (α), wobble angle (θ), virtual torsion angle (ρ), and the hydrogen bond distance d (Op−3 … Np+1). The average values and the flexibility involved in these parameters are evaluated. The correlation among the bend related parameters are estimated. The equilibrium side chain orientations of tryptophan and tyrosine residues are discussed and compared with those found in the recently proposed model of bacteriorhodopsin. Finally, a detailed characterization of the bend in terms of secondary structures such as αI, αII and goniometric helices are discussed, which can be useful in the interpretation of the experimental results on the secondary structures of membrane proteins involving the proline residue. © 1993 Wiley‐Liss, Inc.
Crystallization and preliminary X‐ray diffraction studies of dogfish C‐reactive protein
Authors: Samudzi Cleopas T. , Nguyen Nga Y. , Rubin J. Ronald 
Published: May 2005

AbstractCrystals of dogfish (Mustelus canis) C‐reactive protein were obtained through vapor phase equilibration using the sitting drop rod technique with ammonium sulfate as the precipitating agent. The space group was determined to be P1 (triclinic lattice) with unit cell dimensions of a = 82.91, b = 92.25 and c = 103.40 Å; α = 83.36°, β = 89.76°, and γ = 81.30°. These crystals diffract to about 2.6 Å resolution and contain two hexamers in the asymmetric unit. © 1993 Wiley‐Liss, Inc.
Structural energetics of peptide recognition: Angiotensin II/antibody binding
Authors: Murphy Kenneth P. , Xie Dong , Garcia K. Christopher , Amzel L. Mario , Freire Ernesto 
Published: May 2005

AbstractThe ability to predict the strength of the association of peptide hormones or other ligands with their protein receptors is of fundamental importance in the fields of protein engineering and rational drug design. To form a tight complex between a flexible peptide hormone and its receptor, the large loss of configurational entropy must be overcome. Recently, the crystallographic structure of the complex between angiotensin II and the Fab fragment of a high affinity monoclonal antibody has been determined (Garcia, K. C., Ronco, P. M., Verroust, P. J., Brünger, A. T., Amzel, L. M. Three‐dimensional structure of an angiotensin II–Fab complex at 3 Å: Hormone recognition by an anti‐idiotypic antibody. Science 257:502–507, 1992). In this paper we present a study of the thermodynamics of the association by high sensitivity isothermal titration calorimetry. The results of the experiments indicate that at 30°C the binding is characterized by (1) a ΔH of −8.9 ± 0.7 kcal mol−1, (2) a ΔCp of −240 ± 20 cal K−1 mol−1, and (3) the release of 1.1 ± 0.1 protons per binding site in the pH range 6.0–7.3. Using these values and the previously determined binding constant in phosphate buffer, ΔG at 30°C is estimated as −11 kcal mol−1 and ΔS as 6.9 cal K−1 mol−1. The calorimetric data indicate that binding is favored both enthalpically and entropically. These results have been complemented by structural thermodynamic calculations. The calculated and experimentally determined thermodynamic quantities are in good agreement. Entropically, the loss of configurational entropy is more than compensated by the entropy gain from solvent release associated with the hydrophobic effect. Enthalpically, binding is favored by polar interactions (hydrogen bonding). Consequently, the problem of binding flexible hormones is solved in much the same way as the folding of an unstructured polypeptide chain into a globular protein. © 1993 Wiley‐Liss, Inc.
Successful prediction of the coiled coil geometry of the GCN4 leucine zipper domain by simulated annealing: Comparison to the X‐ray structure
Authors: Nilges Michael , BrüNger Axel T. 
Published: May 2005

AbstractThe recently solved X‐ray structure of the dimerization region (“leucine zipper”) of the yeast transcriptional activator GCN4 (O'Shea, E. K., Klemm, J. D., Kim, P. S., Alber, T. Science 254:539–544, 1991) is compared to previously predicted models which had been obtained by a conformational search procedure employing simulated annealing without any knowledge of the crystal coordinates (Nilges, M., Brünger, A. T. Protein Eng. 4:649–659,1991). During the course of the simulated annealing procedure, the models converged towards the X‐ray structure. The averaged root mean square difference between the models and the X‐ray structure is 1.26 and 1.75 Å for backbone atoms and all nonhydrogen atoms at the dimerization interface, respectively. The local helix–helix crossing angle of the X‐ray structure falls within the range predicted by the models; a slight unwinding of the coiled coil toward the N‐terminal DNA‐binding end of the dimerization region has been correctly predicted. Distance maps between the helices are largely identical. The region around asparagine 20 is asymmetric in the X‐structure and in the models. Surface side chain dihedrals showed a large variation in the models although the χ1, χ2, χ3, χ4 3‐fold dihedrals were correctly predicted in 69, 42, 43, and 44% of the cases, respectively. Phenomenological free energies of dimerization of the models show little correlation with the root mean square difference between the models and the X‐ray structure. © 1993 Wiley‐Liss, Inc.