bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein conformational landscapes: Energy minimization and clustering of a long molecular dynamics trajectory
Authors: Troyer John M. , Cohen Fred E. 
Published: May 2005

AbstractUsing energy minimization and cluster analysis, we have analyzed a 1020 ps molecular dynamics trajectory of solvated bovine pancreatic trypsin inhibitor. Elucidation of conformational sub states in this way both illustrates the degree of conformational convergence in the simulation and reduces the structural data to a tractable subset. The relative movement of structures upon energy minimization was used to estimate the sizes of features on the protein potential energy surface. The structures were analyzed using their pairwise root‐mean‐square Cα deviations, which gave a global measure of conformational changes that would not be apparent by monitoring single degrees of freedom. At time scales of 0.1 ps, energy minimization detected sharp transitions between energy minima separated by 0.1 Å rms deviation. Larger conformational clusters containing these smaller minima and separated by 0.25 Å were seen at 1 ps time scales. Both of these small features of the conformational landscape were characterized by movements in loop regions associated with small, correlated backbone dihedral angle shifts. On a nanosecond time scale, the main features of the protein energy landscape were clusters separated by over 0.7 Å rms deviation, with only seven of these sub states visited over the 1 ns trajectory. These substates, discernible both before and after energy minimization, differ mainly in a monotonic pivot of the loop residues 11–18 over the course of the simulation. This loop contains lysine 17, which specifically binds to trypsin in the active site. The trajectory did not return to previously visited clusters, indicating that this trajectory has not been shown to have completely sampled the conformational substates available to it. Because the apparent convergence to a single region of conformation space depends on both the time scale of observation and the size of the conformational features examined, convergence must be operationally defined within the context of the simulation. © 1995 Wiley‐Liss, Inc.
Determination of the conformation of folding initiation sites in proteins by computer simulation
Authors: Avbelj Franc , Moult John 
Published: May 2005

AbstractExperimental evidence and theoretical models both suggest that protein folding begins by specific short regions of the polypeptide chain intermittently assuming conformations close to their final ones. The independent folding properties and small size of these folding initiation sites make them suitable subjects for computational methods aimed at deriving structure from sequence. We have used a torsion space Monte Carlo procedure together with an all‐atom free energy function to investigate the folding of a set of such sites. The free energy function is derived by a potential of mean force analysis of experimental protein structures. The most important contributions to the total free energy are the local main chain electrostatics, main chain hydrogen bonds, and the burial of nonpolar area. Six proposed independent folding units and four control peptides 11–14 residues long have been investigated. Thirty Monte Carlo simulations were performed on each peptide, starting from different random conformations. Five of the six folding units adopted conformations close to the experimental ones in some of the runs. None of the controls did so, as expected. The generated conformations which are close to the experimental ones have among the lowest free energies encountered, although some less native like low free energy conformations were also found. The effectiveness of the method on these peptides, which have a wide variety of experimental conformations, is encouraging in two ways: First, it provides independent evidence that these regions of the sequences are able to adopt native like conformations early in folding, and therefore are most probably key components of the folding pathways. Second, it demonstrates that available simulation methods and free energy functions are able to produce reasonably accurate structures. Extensions of the methods to the folding of larger portions of proteins are suggested. © 1995 Wiley‐Liss, Inc.
Progress of 1D protein structure prediction at last
Authors: Rost Burkhard , Sander Chris 
Published: May 2005

AbstractAccuracy of predicting protein secondary structure and solvent accessibility from sequence information has been improved significantly by using information contained in multiple sequence alignments as input to a neural 'network system. For the Asilomar meeting, predictions for 13 proteins were generated automatically using the publicly available prediction method PHD. The results confirm the estimate of 72% three‐state prediction accuracy. The fairly accurate predictions of secondary structure segments made the tool useful as a starting point for modeling of higher dimensional aspects of protein structure. © 1995 Wiley‐Liss, Inc.
Confronting the problem of interconnected structural changes in the comparative modeling of proteins
Authors: Samudrala Ram , Pedersen Jan T. , Zhou Huai‐bei , Luo Rui , Fidelis Krzysztof , Moult John 
Published: May 2005

AbstractComparative models of three proteins have been built using a variety of computational methods, heavily supplemented by visual inspection. We consider the accuracy obtained to be worse than expected. A careful analysis of the models shows that a major reason for the poor results is the interconnectedness of the structural differences between the target proteins and the template structures they were modeled from. Side chain conformations are often determined by details of the structure remote in the sequence, and can be influenced by relatively small main chain changes. Almost all of the regions of substantial main chain conformational change interact with at least one other such region, so that they often cannot be modeled independently. Visual inspection is sometimes effective in correcting errors in sequence alignment and in spotting when an alternative template structure is more appropriate. We expect some improvements in the near future through the development of structure‐based sequence alignment tools, side chain interconnectedness rotamer choice algorithms, and a better understanding of the context sensitivity of conformational features. © 1995 Wiley‐Liss, Inc.
Protein structure prediction by threading methods: Evaluation of current techniques
Authors: Lemer Christian M.‐R. , Rooman Marianne J. , Wodak Shoshana J. 
Published: May 2005

AbstractThis paper evaluates the results of a protein structure prediction contest. The predictions were made using threading procedures, which employ techniques for aligning sequences with 3D structures to select the correct fold of a given sequence from a set of alternatives. Nine different teams submitted 86 predictions, on a total of 21 target proteins with little or no sequence homology to proteins of known structure. The 3D structures of these proteins were newly determined by experimental methods, but not yet published or otherwise available to the predictors. The predictions, made from the amino acid sequence alone, thus represent a genuine test of the current performance of threading methods. Only a subset of all the predictions is evaluated here. It corresponds to the 44 predictions submitted for the 11 target proteins seen to adopt known folds. The predictions for the remaining 10 proteins were not analyzed, although weak similarities with known folds may also exist in these proteins. We find that threading methods are capable of identifying the correct fold in many cases, but not reliably enough as yet. Every team predicts correctly a different set of targets, with virtually all targets predicted correctly by at least one team. Also, common folds such as TIM barrels are recognized more readily than folds with only a few known examples. However, quite surprisingly, the quality of the sequence‐structure alignments, corresponding to correctly recognized folds, is generally very poor, as judged by comparison with the corresponding 3D structure alignments. Thus, threading can presently not be relied upon to derive a detailed 3D model from the amino acid sequence. This raises a very intriguing question: how is fold recognition achieved? Our analysis suggests that it may be achieved because threading procedures maximize hydrophobic interactions in the protein core, and are reasonably good at recognizing local secondary structure. © 1995 Wiley‐Liss, Inc.
Homology modeling of histidine‐containing phosphocarrier protein and eosinophil‐derived neurotoxin: Construction of models and comparison with experiment
Authors: Church W. Bret , Palmer Anneliese , Wathey John C. , Kitson David H. 
Published: May 2005

AbstractHomology modeling methods have been used to construct models of two proteins—the histidine‐containing phosphocarrier protein (HPr) from Mycoplasma capricolum and human eosinophil‐derived neurotoxin (EDN). Comparison of the models with the subsequently determined X‐ray crystal structures indicates that the core regions of both proteins are reasonably well reproduced, although the template structures are closer to the X‐ray structures in these regions—possible enhancements are discussed. The conformations of most of the side chains in the core of HPr are well reproduced in the modeled structure. As expected, the conformations of surface side chains in this protein differ significantly from the X‐ray structure. The loop regions of EDN were incorrectly modeled—reasons for this and possible enhancements are discussed. © 1995 Wiley‐Liss, Inc.
Ab initio structure prediction for small polypeptides and protein fragments using genetic algorithms
Authors: Pedersen Jan T. , Moult John 
Published: May 2005

AbstractAb initio folding simulations have been performed on three peptides, using a genetic algorithm‐based search method which operates on a full atom representation. Conformations are evaluated with an empirical force field parameterized by a potential of mean force analysis of experimental structures. The dominant terms in the force field are local and nonlocal main chain electrostatics and the hydrophobic effect. Two of the simulated structures were for fragments of complete proteins (eosinophil‐derived neurotoxin (EDN) and the subtilisin propeptide) that were identified as being likely initiation sites for folding. The experimental structure of one of these (EDN) was subsequently found to be consistent with that prediction (using local hydrophobic burial as the determinant for independent folding). The simulations of the structures of these two peptides were only partly successful. The most successful folding simulation was that of a 22‐residue peptide corresponding to the membrane binding domain of blood coagulation factor VIII (Membind). Three simulations were performed on this peptide and the lowest energy conformation was found to be the most similar to the experimental structure. The conformation of this peptide was determined with a Cα rms deviation of 4.4 Å. Although these simulations were partly successful there are still many unresolved problems, which we expect to be able to address in the next structure prediction experiment. © 1995 Wiley‐Liss, Inc.
Atomic and residue hydrophilicity in the context of folded protein structures
Authors: Kuhn Leslie A. , Swanson Craig A. , Pique Michael E. , Tainer John A. , Getzoff Elizabeth D. 
Published: May 2005

AbstractWater‐protein interactions drive protein folding, stabilize the folded structure, and influence molecular recognition and catalysis. We analyzed the closest protein contacts of 10,837 water molecules in crystallographic structures to define a specific hydrophilicity scale reflecting specific rather than bulk solvent interactions. The tendencies of different atom and residue types to be the nearest protein neighbors of bound water molecules correlated with other hydrophobicity scales, verified the relevance of crystallographically determined water positions, and provided a direct experimental measure of water affinity in the context of the folded protein. This specific hydrophilicity was highly correlated with hydrogen‐bonding capacity, and correlated better with experimental than computationally derived measures of partitioning between aqueous and organic phases. Atoms with related chemistry clustered with respect to the number of bound water molecules. Neutral and negatively charged oxygen atoms were the most hydrophilic, followed by positively‐charged then neutral nitrogen atoms, followed by carbon and sulfur atoms. Agreement between observed side‐chain specific hydrophilicity values and values derived from the atomic hydrophilicity scale showed that hydrophilicity values can be synthesized for different functional groups, such as unusual side or main chains, discontinuous epitopes, and drug molecules. Two methods of atomic hydrophilicity analysis provided a measure of complementarity in the interfaces of trypsin:pancreatic trypsin inhibitor and HIV protease:U‐75875 inhibitor complexes. © 1995 Wiley‐Liss, Inc.
Control of crystal forms of apoferritin by site‐directed mutagenesis
Authors: Takeda Shigeki , Yoshimura Hideyuki , Endo Sigeru , Takahashi Takuya , Nagayama Kuniaki 
Published: May 2005

AbstractSurface charges of protein molecules are not only important to biological functions but also crucial to the molecular assembly responsible for crystallization. Appropriate alteration in the surface charge distribution of a protein molecule induces new molecular alignment in the proper direction in the crystal and, hence, controls the crystal form. Apoferritin molecules are known to crystallize in two‐ and three‐dimensional forms in the presence of cadmium ions, which bridge neighboring protein molecules. Here we report a controlled transformation of the apoferritin 2‐D crystal by site‐directed mutagenesis. In mutant apoferritin, two amino acid residues binding a cadmium‐ion through their negative charge, were replaced by one type of nonionic amino acid residues. The amino acid residues, Asp‐84 and Gln‐86 in the sequence of recombinant (i.e., wild‐type) horse L‐apoferritin, were replaced by Ser. The wild‐type apoferritin yielded a hexagonal lattice 2‐D crystal in the presence of cadmium ions. In contrast, the mutant apoferritin yielded two types of oblique crystals independent of the presence of cadmium ions. Image reconstruction of electron micrographs of the mutant crystals made clear that the mutant apoferritin molecules oriented themselves with the 2‐fold symmetry axis perpendicular to the crystal plane in both crystals, while the wild‐type apoferritin molecules oriented themselves with the 3‐fold symmetry axis perpendicular to the crystal plane. The changes of crystal forms and molecular orientation in the 2‐D crystals were well explained by a change of the electrostatic interactions induced by the mutagenesis. © 1995 Wiley‐Liss, Inc.
Knowledge‐based protein secondary structure assignment
Authors: Frishman Dmitrij , Argos Patrick 
Published: May 2005

AbstractWe have developed an automatic algorithm STRIDE for protein secondary structure assignment from atomic coordinates based on the combined use of hydrogen bond energy and statistically derived backbone torsional angle information. Parameters of the pattern recognition procedure were optimized using designations provided by the crystallographers as a standard‐of‐truth. Comparison to the currently most widely used technique DSSP by Kabsch and Sander (Biopolymers 22:2577‐2637, 1983) shows that STRIDE and DSSP assign secondary structural states in 58 and 31% of 226 protein chains in our data sample, respectively, in greater agreement with the specific residue‐by‐residue definitions provided by the discoverers of the structures while in 11% of the chains, the assignments are the same. STRIDE delineates every 11th helix and every 32nd strand more in accord with published assignments. © 1995 Wiley‐Liss, Inc.
Crystallization and preliminary crystallographic study of human lithostathine
Authors: Pignol David , Bertrand Jay A. , Bernard Jean‐Paul , Verdier Jean‐Michel , Dagorn Jean‐Charles , Fontecilla‐Camps Juan Carlos 
Published: May 2005

AbstractCrystals of human lithostathine, a pancreatic glycoprotein which inhibits the growth and nucleation of calcium carbonate crystals, were grown using PEG 4000 as the precipitating agent. The crystals belong to the hexagonal space group P61 (or its enantiomorph P65) and diffract to 1.55 Å resolution. There is one molecule in the asymmetric unit and the crystals have 39% solvent. © 1995 Wiley‐Liss, Inc.
A method for determining the elemental compositions of daughter ions in simple tandem mass spectrometry spectra
Authors: Bozorgzadeh Mohammed Hossein 
Published: May 2005

AbstractA method has been developed and generalized to determine the elemental compositions of daughter ions in simple MS/MS spectra. To employ the method, it is necessary to take the daughter ion spectra of the m and [m1+1]+ ions, where m is the parent ion and [m1+1]+ is the same ion with a replaced naturally‐occurring heavier isotope of mass 1 greater than that of the main isotope. For each daughter ion produced from m, two may be produced from [m1+1]+; one of these will contain the heavy isotope and the other one will not. The ratio of the abundances of these two daughter ions in the spectrum of [m1+1]+ is equal to the ratio of the probabilities of finding the heavy isotope in the ion fragment or in the corresponding neutral fragment(s), and these probabilities are termed the “relative isotope abundances” of the two fragments. An equation is derived for calculating these relative isotope abundances of the daughter ion versus that of the parent. The effectiveness of the method has been tested by applying it to a compound whose spectrum has daughter ions of known formulae. Errors have been measured, and the limitations of the method assessed. Also, several compounds that could produce daughter ions of more than one possible formula were used as tests of the method.
Sputter yields of ammonium chloride and solid glycerol
Authors: Gillen Greg , Christiansen J. W. , Tsong I. S. T. , Kimball B. , Williams Peter , Cooks R. Graham 
Published: May 2005

AbstractWe have measured the sputtering yields of ammonium chloride and of frozen glycerol films under 8 keV Ar+˙ bombardment using a thin film depth profiling technique. The sputtering yield of ammonium chloride was 34±3 molecules (NH4Cl)/ion; for frozen glycerol the sputter yield was 54±9 molecules/ion. The results constrain possible mechanisms of damage suppression in organic secondary ion mass spectrometry.
Product excitation in collision‐induced dissociative ionization of acetone: Internal energy distribution
Authors: Vékey K. , Brenton A. G. 
Published: May 2005

AbstractCharge stripping of a neutral acetone beam, C3H6O, produced by the unimolecular fragmentation of a proton‐bound dimer by the reaction [(C3H6O)2H]+ → C3H6O +[C3H7O]+, was studied for various target gases. The singly‐charged acetone ions, formed after charge stripping of the neutral acetone beam, contained a significant amount of internal energy (dependent on the collision gas), and its distribution was measured. Collision cross‐sections, total and partial, were measured for charge stripping of acetone neutrals. Comparison of the present results with electron‐transfer processes was also made.
A pulsed time‐of‐flight mass spectrometer for liquid secondary ion mass spectrometry
Authors: Olthoff J. K. , Lys I. A. , Cotter R. J. 
Published: May 2005

AbstractThe design and performance of a new time‐of‐flight mass spectrometer is reported. The instrument combines the advantages of a pulsed drawout TOF analyzer with a liquid secondary ion source. Differences from commercially available pulsed TOF analyzers (Wiley/McLaren type) are discussed with regard to operation with ion desorption from a liquid matrix.
A continuous‐flow probe high performance liquid chromatography interface to a liquid secondary‐ion time‐of‐flight mass spectrometer
Authors: Chen Kai‐Hsien , Cotter Robert J. , Caprioli R. M. 
Published: May 2005

AbstractThe possibilities for using the time‐of‐flight analyzer as a liquid chromatography detector are evaluated using a continuous flow probe and keV ion bombardment on a specially designed time‐of‐flight instrument.
Gas‐phase acidity of nitrobenzene from flowing afterglow bracketing studies
Authors: Cheng Xueheng , Grabowski Joseph J. 
Published: May 2005

AbstractRoom temperature ion/molecule reactions in 0.30 Torr of helium, carried out in a flowing afterglow, show that the gas‐phase acidity of nitrobenzene is intermediate between those of ethanol and isopropanol, in contrast to published high‐pressure mass spectrometer data. The revised gas‐phase acidity of nitrobenzene, ΔHºacid(C6H5NO2) = 377 ± 3 kcal mol−1, is shown to be consistent with known acidifying effects when a hydrogen atom is replaced by a nitro group in a Brönsted acid. Additional reactions involving nitrobenzene or its conjugate base are noted.
Capillary‐zone electrophoresis/fast‐atom bombardment mass spectrometry: Design of an on‐line coaxial continuous‐flow interface
Authors: Moseley M. Arthur , Deterding Leesa J. , Tomer Kenneth B. , Jorgenson James W. 
Published: May 2005

AbstractAn on‐line coaxial continuous‐flow capillary‐zone electrophoresis/fast‐atom bombardment mass spectrometry (CZE/FAB‐MS) interface is described. This interface is shown to be capable of acquiring mass spectra in an online fashion from low femtomole amounts of peptides while maintaining high (hundreds of thousands of plates) electrophoretic separation efficiencies. Active electrophoretic transport of the analytes directly to the FAB probe tip obviates the need for a transfer line from the end of the CZE capillary to this point, and thereby precludes the zone broadening that would otherwise occur both within such a transfer line and in the connections between the CZE column and the transfer line. The capability of acquiring an on‐line tandem mass spectrometry (MS/MS) spectrum of an electrophoretically separated analyte using this interface is also demonstrated.
Comparison of amino acid‐sequence analysis by electron ionization and negative‐ion chemical ionization mass spectrometry
Authors: Reinhard H. , Lauber R. , Schlunegger U. P. 
Published: May 2005

AbstractThe positive electron ionization and negative chemical ionization mass spectra of 15 different derivatives of the tripeptide Phe‐Ala‐Leu have been compared. Total ion currents and ion currents of sequence‐characterizing ions have been measured and compared. The negative‐ion spectra, using 10% carbon dioxide in argon as moderator gas, proved to be simpler and contained more abundant sequence ions than the positive electron ionization spectra.
Separation and identification of intact glucosinolates using direct coupling of high‐performance liquid chromatography with frit to fast‐atom bombardment mass spectrometry
Authors: Kokkonen P. , van der Greef J. , Niessen W. M. A. , Tjaden U. R. , ten Hove G. J. , van de Werken G. 
Published: May 2005

AbstractIntact glucosinolates are separated and identified in standard mixtures and in plant extract of Brussels sprouts by using the liquid chromatography frit to fast‐atom bombardment mass spectrometry technique. The separation of the individual glucosinolates is achieved by using a conventional‐bore high‐performance liquid chromatography column with an aqueous ammonium acetate – acetonitrile gradient. The mandatory flow‐rate reduction is achieved by using a pneumatic splitter. The determination limits are estimated to be below 20 μg/g in plant material for various glucosinolates using the sample pretreatment described.