bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha helix capping in synthetic model peptides by reciprocal side chain–main chain interactions: Evidence for an N terminal “capping box”
Authors: Zhou Hongxing X. , Lyu Pingchiang , Wemmer David E. , Kallenbach Neville R. 
Published: May 2005

AbstractA significant fraction of the amino acids in proteins are alpha helical in conformation. Alpha helices in globular proteins are short, with an average length of about twelve residues, so that residues at the ends of helices make up an important fraction of all helical residues. In the middle of a helix, H‐bonds connect the NH and CO groups of each residue to partners four residues along the chain. At the ends of a helix, the H‐bond potential of the main chain remains unfulfilled, and helix capping interactions involving bonds from polar side chains to the NH or CO of the backbone have been proposed and detected. In a study of synthetic helical peptides, we have found that the sequence Ser‐Glu‐Asp‐Glu stabilizes the alpha helix in a series of helical peptides with consensus sequences. Following the report by Harper and Rose, which identifies SerXaaXaaGlu as a member of a class of common motifs at the N termini of alpha helices in proteins that they refer to as “capping boxes,” we have reexamined the side chain–main chain interactions in a varient sequence using 1H NMR, and find that the postulated reciprocal side chain‐backbone bonding between the first Ser and last Glu side chains and their peptide NH partners can be resolved: Deletion of two residues N terminal to the Ser‐Glu‐Asp‐Glu sequence in these peptides has no effect on the initiation of helical structure, as defined by two‐dimensional (2D) NMR experiments on this variant. Thus the capping box sequence Ser‐Glu‐Asp‐Glu inhibits N terminal fraying of the N terminus of alpha helix in these peptides, and shows the side chain–main chain interactions proposed by Harper and Rose. It thus acts as a helix initiating signal. Since normal a helix cannot propagate beyond the N terminus of this structure, the box acts as a termination signal in this direction as well. © 1994 John Wiley & Sons, Inc.
The Structure of Trypanosoma cruzitrypanothione Reductase in the Oxidized and NADPH Reduced State
Authors: Lantwin Christina B. , Schlichting Ilme , Kabsch Wolfgang , Pai Emil F. , Krauth‐Siegel R. Luise 
Published: May 2005

AbstractThe three‐dimensional structure of trypanothione reductase (TR) (EC 1.6.4.8) from Trypanosoma cruzi has been solved at 0.33 nm resolution by molecular replacement using the structure of C. fasciculata TR as a starting model. Elucidation of the T. cruzi TR structure represents the first step in the rational design of a drug against Chagas' disease. The structure of T. cruzi TR is compared with those of C. fasciculata TR as well as human and E. coli glutathione reductase (GR). In the FAD‐binding domain, TR has two insertions, each about 10 residues long, which do not occur in GR. The first one is a rigid loop stabilizing the position of helix 91–117 which is responsible for the wider active site of TR as compared to GR. The second insertion does not occur where it is predicted by sequence alignment; rather the residues extend three strands of the 4‐stranded β‐sheet by one or two residues each. This increases the number of hydrogen bonds within the sheet structure. The structure of the NADPH.TR complex has been solved at 0.33 nm resolution. The nicotinamide ring is sandwiched between the flavin ring and the side chain of Phe‐198 which undergoes the same conformational change upon coenzyme binding as Tyr‐197 in GR. In addition to Arg‐222 and Arg‐228, which are conserved in TR and GR, Tyr‐221—the last residue of the second β‐sheet strand of the βαβ dinucleotide binding fold—is in hydrogen bonding distance to the 2′ phosphate group of NADPH. © 1994 John Wiley & Sons, Inc.
Correlated mutations and residue contacts in proteins
Authors: Göbel Ulrike , Sander Chris , Schneider Reinhard , Valencia Alfonso 
Published: May 2005

AbstractThe maintenance of protein function and structure constrains the evolution of amino acid sequences. This fact can be exploited to interpret correlated mutations observed in a sequence family as an indication of probable physical contact in three dimensions. Here we present a simple and general method to analyze correlations in mutational behavior between different positions in a multiple sequence alignment. We then use these correlations to predict contact maps for each of 11 protein families and compare the result with the contacts determined by crystallography. For the most strongly correlated residue pairs predicted to be in contact, the prediction accuracy ranges from 37 to 68% and the improvement ratio relative to a random prediction from 1.4 to 5.1. Predicted contact maps can be used as input for the calculation of protein tertiary structure, either from sequence information alone or in combination with experimental information. © 1994 John Wiley & Sons, Inc.
Monte carlo simulations of protein folding. I. Lattice model and interaction scheme
Authors: Kolinski Andrzej , Skolnick Jeffrey 
Published: May 2005

AbstractA new hierarchical method for the simulation of the protein folding process and the de novo prediction of protein three‐dimensional structure is proposed. The reduced representation of the protein α‐carbon backbone employs lattice discretizations of increasing geometrical resolution and a single ball representation of side chain rotamers. In particular, coarser and finer lattice backbone descriptions are used. The coarser (finer) lattice represents Cα traces of native proteins with an accuracy of 1.0 (0.7) Å rms. Folding is simulated by means of very fast Monte Carlo lattice dynamics. The potential of mean force, predominantly of statistical origin, contains several novel terms that facilitate the cooperative assembly of secondary structure elements and the cooperative packing of the side chains. Particular contributions to the interaction scheme are discussed in detail. In the accompanying paper (Kolinski, A., Skolnick, J. Monte Carlo simulation of protein folding. II. Application to protein A, ROP, and crambin. Proteins 18:353–366, 1994), the method is applied to three small globular proteins. © 1994 John Wiley & Sons, Inc.
The role of arginine 143 in the electrostatics and mechanism of Cu, Zn superoxide dismutase: Computational and experimental evaluation by mutational analysis
Authors: Fisher Cindy L. , Cabelli Diane E. , Tainer John A. , Hallewell Robert A. , Getzoff Elizabeth D. 
Published: May 2005

AbstractCu, Zn superoxide dismutase protects cells from oxidative damage by removing superoxide radicals in one of the fastest enzyme reactions known. The redox reaction at the active‐site Cu ion is rate‐limited by diffusion and enhanced by electrostatic guidance. To quantitatively define the electrostatic and mechanistic contributions of sequence‐invariant Arg‐143 in human Cu, Zn superoxide dismutase, single‐site mutants at this position were investigated experimentally and computationally. Rate constants for several Arg‐143 mutants were determined at different pH and ionic strength conditions using pulse radiolytic methods and compared to results from Brownian dynamics simulations. At physiological pH, substitution of Arg‐143 by Lys caused a 2‐fold drop in rate, neutral substitutions (Ile, Ala) reduced the rate about 10‐fold, while charge‐reversing substitutions (Asp, Glu) caused a 100‐fold decrease. Position 143 mutants showed pH dependencies not seen in other mutants. At low pH, the acidic residue mutations exhibited pro‐tonation/deprotonation effects. At high pH, all enzymes showed typical decreases in rate except the Lys mutant in which the rate dropped off at an unusually low pH. Increasing ionic strength at acidic pH decreased the rates of the wild‐type enzyme and Lys mutant, while the rate of the Glu mutant was unaffected. Increasing ionic strength at higher pH (>10) increased the rates of the Lys and Glu mutants while the rate of the wild‐type enzyme was unaffected. Reaction simulations with Brownian dynamics incorporating electrostatic effects tested computational predictability of ionic strength dependencies of the wild‐type enzyme and the Lys, Ile, and Glu mutants. The calculated and experimental ionic strength profiles gave similar slopes in all but the Glu mutant, indicating that the electrostatic attraction of the substrate is accurately modeled. Differences between the calculated and experimental rates for the Glu and Lys mutants reflect the mechanistic contribution of Arg‐143. Results from this joint analysis establish that, aside from the Cu ligands, Arg‐143 is the single most important residue in Cu, Zn superoxide dismutase both electrostatically and mechanistically, and provide an explanation for the evolutionary selection of arginine at position 143. © 1994 Wiley‐Liss, Inc.
Crystallization of a fragment of human fibronectin: Introduction of methionine by site‐directed mutagenesis to allow phasing via selenomethionine
Authors: Leahy Daniel J. , Erickson Harold P. , Aukhil Ikramuddin , Joshi Paritosh , Hendrickson Wayne A. 
Published: May 2005

AbstractCrystals of a fragment of human fibronectin encompassing the 7th through the RGD‐containing 10th type III repeats (FN7–10) have been produced with protein expressed in E. coli. The crystals are monoclinic with one molecule in the asymmetric unit and diffract to beyond 2.0 Å Bragg spacings. A mutant FN7–10 was produced in which three methionines, in addition to the single native methionine already present, have been introduced by site‐directed mutagenesis. Diffraction‐quality crystals of this mutant protein have been grown in which methionine was replaced with selenomethionine. The introduction of methionine by site‐directed mutagenesis to allow phasing from selenomethionyl‐substituted crystals is shown to be feasible by this example and is proposed as a general approach to solving the crystallographic phase problem. Strategies for selecting propitious sites for methionine mutations are discussed. © 1994 Wiley‐Liss, Inc.
Crystallization and preliminary X‐ray crystallographic analysis of phospholipid transfer protein from maize seedlings
Authors: Shin Dong Hae , Hwang Kwang Yeon , Kim Kyeong Kyu , Kim Sangsoo , Sweet Robert M. , Suh Se Won 
Published: May 2005

AbstractPhospholipid transfer protein from maize seedlings has been crystallized using trisodium citrate as precipitant. The crystal belongs to the orthorhombic space group P212121 with unit cell dimensions of a = 24.46 Å, b = 49.97 Å, and c = 69.99 Å. The presence of one molecule in the asymmetric unit gives a crystal volume per protein mass (Vm) of 2.36 Å 3/Da and a solvent content of 48% by volume. The X‐ray diffraction pattern extends at least to 1.6 Å Bragg spacing when exposed to both CuKα and synchrotron X‐rays. A set of X‐ray data to approximately 1.9 Å Bragg spacing has been collected from a native crystal. © 1994 Wiley‐Liss, Inc.
Recognition of distantly related proteins through energy calculations
Authors: Abagyan Ruben , Frishman Dmitrij , Argos Patrick 
Published: May 2005

AbstractA new method to detect remote relationships between protein sequences and known three‐dimensional structures based on direct energy calculations and without reliance on statistics has been developed. The likelihood of a residue to occupy a given position on the structural template was represented by an estimate of the stabilization free energy made after explicit prediction of the substituted side chain conformation. The profile matrix derived from these energy values and modified by increasing the residue self‐exchange values successfully predicted compatibility of heatshock protein and globin sequences with the three‐dimensional structures of actin and phycocyanin, respectively, from a full protein sequence databank search. The high sensitivity of the method makes it a unique tool for predicting the three‐dimensional fold for the rapidly growing number of protein sequences. © 1994 Wiley‐Liss, Inc.
Accuracy of protein flexibility predictions
Authors: Vihinen Mauno , Torkkila Esa , Riikonen Pentti 
Published: May 2005

AbstractProtein structural flexibility is important for catalysis, binding, and allostery. Flexibility has been predicted from amino acid sequence with a sliding window averaging technique and applied primarily to epitope search. New prediction parameters were derived from 92 refined protein structures in an unbiased selection of the Protein Data Bank by developing further the method of Karplus and Schulz (Naturwissenschaften 72:212–213, 1985). The accuracy of four flexibility prediction techniques was studied by comparing atomic temperature factors of known three‐dimensional protein structures to predictions by using correlation coefficients. The size of the prediction window was optimized for each method. Predictions made with our new parameters, using an optimized window size of 9 residues in the prediction window, were giving the best results. The difference from another previously used technique was small, whereas two other methods were much poorer. Applicability of the predictions was also tested by searching for known epitopes from amino acid sequences. The best techniques predicted correctly 20 of 31 continuous epitopes in seven proteins. Flexibility parameters have previously been used for calculating protein average flexibility indices which are inversely correlated to protein stability. Indices with the new parameters showed better correlation to protein stability than those used previously; furthermore they had relationship even when the old parameters failed. © 1994 Wiley‐Liss, Inc.
Molecular dynamics simulation of the docking of substrates to proteins
Authors: Di Nola Alfredo , Roccatano Danilo , Berendsen Herman J. C. 
Published: May 2005

AbstractA simple method is described to perform docking of subtrates to proteins or probes to receptor molecules by a modification of molecular dynamics simulations. The method consists of a separation of the center‐of‐mass motion of the substrate from its internal and rotational motions, and a separate coupling to different thermal baths for both types of motion of the substrate and for the motion of the receptor. Thus the temperatures and the time constants of coupling to the baths can be arbitrarily varied for these three types of motion, allowing either a frozen or a flexible receptor and allowing control of search rate without disturbance of internal structure. In addition, an extra repulsive term between substrate and protein was applied to smooth the interaction. The method was applied to a model substrate docking onto a model surface, and to the docking of phosphocholine onto immunoglobulin McPC603, in both cases with a frozen receptor. Using transrational temperatures of the substrate in the range of 1300–1700 K and room temperature for the internal degrees of freedom of the substrate, an efficient nontrapping exploratory search (“helicopter view”) is obtained, which visits the correct binding sites. Low energy conformations can then be further investigated by separate search or by dynamic simulated annealing. In both cases the correct minima were identified. The possibility to work with flexible receptors is discussed. © 1994 Wiley‐Liss, Inc.
Structural modeling and electrostatic properties of aspartate transcarbamylase from Saccharomyces cerevisiae
Authors: Villoutreix Bruno O. , Spassov Velin Z. , Atanasov Boris P. , Hervé Guy , Ladjimi Moncef M. 
Published: May 2005

AbstractIn Saccharomyces cerevisiae the first two reactions of the pyrimidine pathway are catalyzed by a multifunctional protein which possesses carbamylphosphate synthetase and aspartate transcarbamylase activities. Genetic and proteolysis studies suggested that the ATCase activity is carried out by an independently folded domain. In order to provide structural information for ongoing mutagenesis studies, a model of the three‐dimensional structure of this domain was generated on the basis of the known X‐ray structure of the related catalytic subunit from E. coli ATCase. First, a model of the catalytic monomer was built and refined by energy minimization. In this structure, the conserved residues between the two proteins were found to constitute the hydrophobic core whereas almost all the mutated residues are located at the surface. Then, a trimeric structure was generated in order to build the active site as it lies at the interface between adjacent chains in the E. coli catalytic trimer. After docking a bisubstrate analog into the active site, the whole structure was energy minimized to regularize the interactions at the contact areas between subunits. The resulting model is very similar to that obtained for the E. coli catalytic trimer by X‐ray crystallography, with a remarkable conservation of the structure of the active site and its vicinity. Most of the interdomain and intersubunit interactions that are essential for the stability of the E. coli catalytic trimer are maintained in the yeast enzyme even though there is only 42% identity between the two sequences. Free energy calculations indicate that the trimeric assembly is more stable than the monomeric form. Moreover an insertion of four amino acids is localized in a loop which, in E. coli ATCase, is at the surface of the protein. This insertion exposes hydrophobic residues to the solvent. Interestingly, such an insertion is present in all the eukaryotic ATCase genes sequenced so far, suggesting that this region is interacting with another domain of the multifunctional protein. © 1994 Wiley‐Liss, Inc.
Torsion angle dynamics: Reduced variable conformational sampling enhances crystallographic structure refinement
Authors: Rice Luke M. , BrüNger Axel T. 
Published: May 2005

AbstractA reduced variable conformational sampling strategy for macromolecules based on molecular dynamics in torsion angle space is evaluated using crystallographic refinement as a prototypical search problem. Bae and Haug's algorithm for constrained dynamics [Bae, D. S., Haug, E. J. A recursive formulation for constrained mechanical system dynamics. Mech. Struct. Mach. 15:359–382, 1987], originally developed for robotics, was used. Their formulation solves the equations of motion exactly for arbitrary holonomic constraints, and hence differs from commonly used approximation algorithms. It uses gradients calculated in Cartesian coordinates, and thus also differs from internal coordinate formulations. Molecular dynamics can be carried out at significantly higher temperatures due to the elimination of the high frequency bond and angle vibrations. The sampling strategy presented here combines high temperature torsion angle dynamics with repeated trajectories using different initial velocities. The best solutions can be identified by the free R value, or the R value if experimental phase information is appropriately included in the refinement. Applications to crystallographic refinement show a significantly increased radius of convergence over conventional techniques. For a test system with diffraction data to 2 Å resolution, slow‐cooling protocols fail to converge if the backbone atom root mean square (rms) coordinate deviation from the crystal structure is greater than 1.25 Å, but torsion angle refinement can correct backbone atom rms coordinate deviations up to approximately 1.7 Å. © 1994 Wiley‐Liss, Inc.
Crystallographic analysis of oxygenated and deoxygenated states of arthropod hemocyanin shows unusual differences
Authors: Magnus Karen A. , Hazes Bart , Ton‐That Hoa , Bonaventura Celia , Bonaventura Joseph , Hol Wim G. J. 
Published: May 2005

AbstractThe X‐ray structure of an oxygenated hemocyanin molecule, subunit II of Limulus polyphemus hemocyanin, was determined at 2.4 Å resolution and refined to a crystallographic R‐factor of 17.1%. The 73‐kDa subunit crystallizes with the symmetry of the space group R32 with one subunit per asymmetric unit forming hexamers with 32 point group symmetry. Molecular oxygen is bound to a dinuclear copper center in the protein's second domain, symmetrically between and equidistant from the two copper atoms. The copper‐copper distance in oxygenated Limulus hemocyanin is 3.6 ± 0.2 Å, which is surprisingly 1 Å less than that seen previously in deoxygenated Limulus polyphemus subunit II hemocyanin (Hazes et al., Protein Sci. 2:597, 1993). Away from the oxygen binding sites, the tertiary and quaternary structures of oxygenated and deoxygenated Limulus subunit II hemocyanins are quite similar. A major difference in tertiary structures is seen, however, when the Limulus structures are compared with deoxygenated Panulirus interruptus hemocyanin (Volbeda, A., Hol, W. G. J. J. Mol. Biol. 209:249, 1989) where the position of domain 1 is rotated by 8° with respect to domains 2 and 3. We postulate this rotation plays an important role in cooperativity and regulation of oxygen affinity in all arthropod hemocyanins. © 1994 Wiley‐Liss, Inc.
A prediction of the secondary structure of the pleckstrin homology domain
Authors: Jenny Thomas F. , Benner Steven A. 
Published: May 2005

AbstractA consensus prediction for the secondary structure of the pleckstrin homology (PH) domain is presented. The prediction is based on an analysis of patterns of conservation and variation of homologous protein sequences. The structure is predicted to be formed largely from beta strands with a single alpha helix. © 1994 Wiley‐Liss, Inc.
Protein stability parameters measured by hydrogen exchange
Authors: Bai Yawen , Milne John S. , Mayne Leland , Englander S. Walter 
Published: May 2005

AbstractThe hydrogen exchange (HX) rates of the slowest peptide group NH hydrogens in oxidized cytochrome c (equine) are controlled by the transient global unfolding equilibrium. These rates can be measured by one‐dimensional nuclear magnetic resonance and used to determine the thermodynamic parameters of global unfolding at mild solution conditions well below the melting transition. The free energy for global unfolding measured by hydrogen exchange can differ from values found by standard denaturation methods, most notably due to the slow cis‐trans isomerization of the prolyl peptide bond. This difference can be quantitatively calculated from basic principles. Even with these corrections, HX experiments at low denaturant concentration measure a free energy of protein stability that rises above the usual linear extrapolation from denaturation data, as predicted by the denaturant binding model of Tanford. © 1994 Wiley‐Liss, Inc.
A special‐purpose computer for molecular dynamics: GRAPE‐2A
Authors: Ito Tomoyoshi , Fukushige Toshiyuki , Makino Junichiro , Ebisuzaki Toshikazu , Okumura Sachiko K. , Sugimoto Daiichiro , Miyagawa Hiroo , Kitamura Kunihiro 
Published: May 2005

AbstractMolecular dynamics simulations have been extensively used in research of proteins. Since these simulations are quite computer intensive, their acceleration is of main interest of the research. In molecular dynamics simulations, almost all computing time is consumed in calculating the forces between particles, e.g., Coulomb and van der Waals forces. We have designed and built GRAPE‐2A (GRAvity PipE 2A), a special‐purpose computer for use in simulations of classical many‐body systems. GRAPE‐2A calculates forces exerted on a particle from the other particles. GRAPE‐2A can calculate force of an arbitrary functional form of a central force. The host computer, which is connected to GRAPE‐2A through the VME bus, performs other calculations such as time integration. The peak speed of GRAPE‐2A is 180 Mflops. We can also stimulate systems with periodic boundary conditions by the Ewald method, using GRAPE‐2A and another special‐purpose computer, WINE (Wave space INtegrator for the Ewald method). © 1994 Wiley‐Liss, Inc.