bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural determinants of species‐selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies
Authors: Kaufmann Kristian W. , Dawson Eric S. , Henry L. Keith , Field Julie R. , Blakely Randy D. , Meiler Jens 
Published: August 2008

AbstractTo identify potential determinants of substrate selectivity in serotonin (5‐HT) transporters (SERT), models of human and Drosophila serotonin transporters (hSERT, dSERT) were built based on the leucine transporter (LeuTAa) structure reported by Yamashita et al. (Nature 2005;437:215–223), PBDID 2A65. Although the overall amino acid identity between SERTs and the LeuTAa is only 17%, it increases to above 50% in the first shell of the putative 5‐HT binding site, allowing de novo computational docking of tryptamine derivatives in atomic detail. Comparison of hSERT and dSERT complexed with substrates pinpoints likely structural determinants for substrate binding. Forgoing the use of experimental transport and binding data of tryptamine derivatives for construction of these models enables us to critically assess and validate their predictive power: A single 5‐HT binding mode was identified that retains the amine placement observed in the LeuTAa structure, matches site‐directed mutagenesis and substituted cysteine accessibility method (SCAM) data, complies with support vector machine derived relations activity relations, and predicts computational binding energies for 5‐HT analogs with a significant correlation coefficient (R = 0.72). This binding mode places 5‐HT deep in the binding pocket of the SERT with the 5‐position near residue hSERT A169/dSERT D164 in transmembrane helix 3, the indole nitrogen next to residue Y176/Y171, and the ethylamine tail under residues F335/F327 and S336/S328 within 4 Å of residue D98. Our studies identify a number of potential contacts whose contribution to substrate binding and transport was previously unsuspected. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Dissection, residue conservation, and structural classification of protein‐DNA interfaces
Authors: Biswas Sumit , Guharoy Mainak , Chakrabarti Pinak 
Published: August 2008

AbstractThe basic DNA‐binding modules of 128 protein‐DNA interfaces have been analyzed. Although these are less planar, like the protein–protein interfaces, the protein‐DNA interfaces can also be dissected into core regions in which all the fully‐buried atoms are located, and rim regions having atoms with residual accessibilities. The sequence entropy of the core residues is smaller than those in the rim, indicating that the former are better conserved and possibly contribute more towards the binding free energy, as has been implicated in protein–protein interactions. On the protein side, 1014 Å2 of the surface is buried of which 63% belong to the core. There are some differences in the propensities of residues to occur in the core and the rim. In the DNA strands, the nucleotide(s) containing fully‐buried atoms in all three components usually occupy central positions of the binding region. A new classification scheme for the interfaces has been introduced based on the composition of secondary structural elements of residues and the results compared with the conventional classification of DNA‐binding proteins, as well as the protein class of the molecule. It appears that a common framework may be developed to understand both protein–protein and protein‐DNA interactions. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Cell cycle kinases predicted from conserved biophysical properties
Authors: Wrzeszczynski Kazimierz O. , Rost Burkhard 
Published: August 2008

AbstractMachine‐learning techniques can classify functionally related proteins where homology‐transfer as well as sequence and structure motifs fail. Here, we present a method that aimed at complementing homology‐transfer in the identification of cell cycle control kinases from sequence alone. First, we identified functionally significant residues in cell cycle proteins through their high sequence conservation and biophysical properties. We then incorporated these residues and their features into support vector machines (SVM) to identify new kinases and more specifically to differentiate cell cycle kinases from other kinases and other proteins. As expected, the most informative residues tend to be highly conserved and tend to localize in the ATP binding regions of the kinases. Another observation confirmed that ATP binding regions are typically not found on the surface but in partially buried sites, and that this fact is correctly captured by accessibility predictions. Using these highly conserved, semi‐buried residues and their biophysical properties, we could distinguish cell cycle S/T kinases from other kinase families at levels around 70–80% accuracy and 62–81% coverage. An application to the entire human proteome predicted at least 97 human proteins with limited previous annotations to be candidates for cell cycle kinases. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Calcium binding to the purple membrane: A molecular dynamics study
Authors: Wassenaar Tsjerk A. , Daura Xavier , Padrós Esteve , Mark Alan E. 
Published: August 2008

AbstractThe purple membrane (PM) is a specialized membrane patch found in halophilic archaea, containing the photoreceptor bacteriorhodopsin (bR). It is long known that calcium ions bind to the PM, but their position and role remain elusive to date. Molecular dynamics simulations in conjunction with a highly detailed model of the PM have been used to investigate the stability of calcium ions placed at three proposed cation binding sites within bR, one near the Schiff base, one in the region of the proton release group, and one near Glu9. The simulations suggest that, of the sites investigated, the binding of calcium ions was most likely at the proton release group. Binding in the region of the Schiff base, while possible, was associated with significant changes in local geometry. Calcium ions placed near Glu9 in the interior of bR (simultaneously to a Ca2+ near the Schiff base and another one near the Glu194–Glu204 site) were not stable. The results obtained are discussed in relation to recent experimental observations and theoretical considerations. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Information theory provides a comprehensive framework for the evaluation of protein structure predictions
Authors: Swanson Rosemarie , Vannucci Marina , Tsai Jerry W. 
Published: August 2008

AbstractProtein structure prediction has a number of important ad hoc similarity measures for evaluating predictions, but would benefit from a measure that is able to provide a common framework for a broad range of comparisons. Here we show that a mutual information‐like measure can provide a comprehensive framework for evaluating protein structure prediction of all types. We discuss the concept of information, its application to secondary structure, and the obstacle to applying it to 3D structure. On the basis of the insights from the secondary structure case, we present an approach to work around the 3D difficulties, and develop a method to measure the mutual information provided by a 3D structure prediction. We integrate the evaluation of all types of protein structure prediction into a single framework, and compare the amount of information provided by various prediction methods, including secondary structure prediction. Within this broadened framework, the idea that structure is better preserved than sequence during evolution is evaluated quantitatively for the globin family. A nearly perfect sequence match in the globin family corresponds to about 300 bits of information, whereas a nearly perfect structural match for the same two proteins corresponds to about 2500 bits of information, where bits of information describes the probability of obtaining a match of similar closeness by chance. Mutual information provides both a theoretical basis for evaluating structure similarity and an explanatory surround for existing similarity measures. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Protein cutoff scanning: A comparative analysis of cutoff dependent and cutoff free methods for prospecting contacts in proteins
Authors: da Silveira Carlos H. , Pires Douglas E. V. , Minardi Raquel C. , Ribeiro Cristina , Veloso Caio J. M. , Lopes Julio C. D. , Meira Wagner , Neshich Goran , Ramos Carlos H. I. , Habesch Raul , Santoro Marcelo M. 
Published: August 2008

AbstractIn this study, we carried out a comparative analysis between two classical methodologies to prospect residue contacts in proteins: the traditional cutoff dependent (CD) approach and cutoff free Delaunay tessellation (DT). In addition, two alternative coarse‐grained forms to represent residues were tested: using alpha carbon (CA) and side chain geometric center (GC). A database was built, comprising three top classes: all alpha, all beta, and alpha/beta. We found that the cutoff value at about 7.0 Å emerges as an important distance parameter. Up to 7.0 Å, CD and DT properties are unified, which implies that at this distance all contacts are complete and legitimate (not occluded). We also have shown that DT has an intrinsic missing edges problem when mapping the first layer of neighbors. In proteins, it may produce systematic errors affecting mainly the contact network in beta chains with CA. The almost‐Delaunay (AD) approach has been proposed to solve this DT problem. We found that even AD may not be an advantageous solution. As a consequence, in the strict range up to 7.0 Å, the CD approach revealed to be a simpler, more complete, and reliable technique than DT or AD. Finally, we have shown that coarse‐grained residue representations may introduce bias in the analysis of neighbors in cutoffs up to 6.8 Å, with CA favoring alpha proteins and GC favoring beta proteins. This provides an additional argument pointing to the value of 7.0 Å as an important lower bound cutoff to be used in contact analysis of proteins. Proteins 2009. © 2008 Wiley‐Liss, Inc.
The utility of molecular dynamics simulations for understanding site‐directed mutagenesis of glycine residues in biotin carboxylase
Authors: Bordelon Tee , Nilsson Lill Sten O. , Waldrop Grover L. 
Published: August 2008

AbstractBiotin carboxylase from Escherichia coli catalyzes the ATP‐dependent carboxylation of biotin and is one component of the multienzyme complex acetyl‐CoA carboxylase, which catalyzes the committed step in long‐chain fatty acid synthesis. Comparison of the crystal structures of biotin carboxylase in the absence and presence of ATP showed a central B‐domain closure when ATP was bound. Peptidic NH groups from two active site glycine residues (Gly165 and Gly166) that form hydrogen bonds to the phosphate oxygens of ATP were postulated to act as a “trigger” for movement of the B‐domain. The function of these two glycine residues in the catalytic mechanism was studied by disruption of the hydrogen bonds using site‐directed mutagenesis. Both single (G165V) and (G166V) and double mutants (G165V‐G166V) were constructed. The mutations did not affect the maximal velocity of a partial reaction, the bicarbonate‐dependent ATPase activity. This suggests that the peptidic NH groups of Gly165 and Gly166 are not triggers for domain movement. However, the Km values for ATP for each of the mutants was increased over 40‐fold when compared with wild‐type indicating the peptidic NH groups of Gly165 and Gly166 play a role in binding ATP. Consistent with ATP binding, the maximal velocity for the biotin‐dependent ATPase activity (i.e. the complete reaction) was decreased over 100‐fold suggesting the mutations have misaligned the reactants for optimal catalysis. Molecular dynamics studies confirm perturbation of the hydrogen bonds from the mutated residues to ATP, whereas the double mutant exhibits antagonistic effects such that hydrogen bonding from residues 165 and 166 to ATP is similar to that in the wild‐type. Consistent with the site‐directed mutagenesis results the molecular dynamics studies show that ATP is misaligned in the mutants. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Prediction of helix–helix contacts and interacting helices in polytopic membrane proteins using neural networks
Authors: Fuchs Angelika , Kirschner Andreas , Frishman Dmitrij 
Published: August 2008

AbstractDespite rapidly increasing numbers of available 3D structures, membrane proteins still account for less than 1% of all structures in the Protein Data Bank. Recent high‐resolution structures indicate a clearly broader structural diversity of membrane proteins than initially anticipated, motivating the development of reliable structure prediction methods specifically tailored for this class of molecules. One important prediction target capturing all major aspects of a protein's 3D structure is its contact map. Our analysis shows that computational methods trained to predict residue contacts in globular proteins perform poorly when applied to membrane proteins. We have recently published a method to identify interacting α‐helices in membrane proteins based on the analysis of coevolving residues in predicted transmembrane regions. Here, we present a substantially improved algorithm for the same problem, which uses a newly developed neural network approach to predict helix–helix contacts. In addition to the input features commonly used for contact prediction of soluble proteins, such as windowed residue profiles and residue distance in the sequence, our network also incorporates features that apply to membrane proteins only, such as residue position within the transmembrane segment and its orientation toward the lipophilic environment. The obtained neural network can predict contacts between residues in transmembrane segments with nearly 26% accuracy. It is therefore the first published contact predictor developed specifically for membrane proteins performing with equal accuracy to state‐of‐the‐art contact predictors available for soluble proteins. The predicted helix–helix contacts were employed in a second step to identify interacting helices. For our dataset consisting of 62 membrane proteins of solved structure, we gained an accuracy of 78.1%. Because the reliable prediction of helix interaction patterns is an important step in the classification and prediction of membrane protein folds, our method will be a helpful tool in compiling a structural census of membrane proteins. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV‐1 protease
Authors: Lexa Katrina W. , Damm Kelly L. , Quintero Jerome J. , Gestwicki Jason E. , Carlson Heather A. 
Published: August 2008

AbstractThe 1TW7 crystal structure of HIV‐1 protease shows the flaps placed wider and more open than what is seen in other examples of the semi‐open, apo form. It has been proposed that this might be experimental evidence of allosteric control, because crystal packing creates contacts to the “elbow region” of the protease, which may cause deformation of the flaps. Recent dynamics simulations have shown that the conformation seen in 1TW7 relaxes into the typical semi‐open conformation in the absence of the crystal contacts, definitively showing that the crystal contacts cause the deformation (Layten et al., J Am Chem Soc 2006;128:13360–13361). However, this does not prove or disprove allosteric modulation at the elbow. In this study, we have conducted additional simulations, supplemented with experimental testing, to further probe the possibility of 1TW7 providing an example of allosteric control of the flap region. We show that the contacts are unstable and do not restrict the conformational sampling of the flaps. The deformation seen in the 1TW7 crystal structure is simply opportunistic crystal packing and not allosteric control. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Identification of putative, stable binding regions through flexibility analysis of HIV‐1 gp120
Authors: Tan Hepan , Rader A. J. 
Published: August 2008

AbstractThe acquired‐immunodeficiency syndrome has evolved into a major worldwide epidemic. Significant effort has been made in the development of antiviral therapies. A new strategy for vaccine and drug design that complements the existing cocktail therapy is to target entry of the human immunodeficiency virus (HIV). Such an approach provides the advantage of interfering with multiple intermediates in this multi‐step process. The extraordinary conformational flexibility, glycosylation, and strain variations of viral glycoprotein gp120 cause general viral evasion of humoral immune response and thus complicate the development of an effective vaccine. Especially difficult to define are the conformation of gp120 before CD4 engagement as well as the relative orientations of the V1/V2 and V3 loops with respect to the inner and outer domains. In this study, we used Floppy Inclusion and Rigid Substructure Topography (FIRST), a program based on graph theory, to analyze the flexibility and rigidity of all known HIV‐1 gp120 structures. A flexibility index is used to describe and compare the spatial distribution of protein flexibility and rigidity of these structures in isolation and in complex with CD4, CD4‐mimics, and neutralizing antibodies. Using this flexibility analysis, we identified a universal rigid region (the α2 helix) as well as the consensus largest rigid cluster involving a β‐sheet located on the coreceptor binding face. Both of these regions may serve as stable targets for vaccine design and drug discovery. Detailed comparisons of the changes in flexibility based on strain variations, stabilizing mutations, binding features of CD4 mimics, and impact of b12 binding are reported. Proteins 2009. © 2008 Wiley‐Liss, Inc.
An efficient real‐time method of analysis for non‐coherent fault trees
Authors: Remenyte‐Prescott Rasa , Andrews John D. 
Published: August 2008

AbstractFault tree analysis is commonly used to assess the reliability of potentially hazardous industrial systems. The type of logic is usually restricted to AND and OR gates, which makes the fault tree structure coherent. In non‐coherent structures not only components' failures but also components' working states contribute to the failure of the system. The qualitative and quantitative analyses of such fault trees can present additional difficulties when compared with the coherent versions. It is shown that the binary decision diagram (BDD) method can overcome some of the difficulties in the analysis of non‐coherent fault trees. This paper presents the conversion process of non‐coherent fault trees to BDDs. A fault tree is converted to a BDD that represents the system structure function (SFBDD). An SFBDD can then be used to quantify the system failure parameters but is not suitable for the qualitative analysis. Established methods, such as the meta‐products BDD method, the zero‐suppressed BDD (ZBDD) method and the labelled BDD (L‐BDD) method, require an additional BDD that contains all prime implicant sets. The process using some of the methods can be time consuming and is not very efficient. In addition, in real‐time applications the conversion process is less important and the requirement is to provide an efficient analysis. Recent uses of the BDD method are for real‐time system prognosis. In such situations as events happen, or failures occur, the prediction of mission success is updated and used in the decision‐making process. Both qualitative and quantitative assessments are required for the decision making. Under these conditions fast processing and small storage requirements are essential. Fast processing is a feature of the BDD method. It would be advantageous if a single BDD structure could be used for both the qualitative and quantitative analyses. Therefore, a new method, the ternary decision diagram (TDD) method, is presented in this paper, where a fault tree is converted to a TDD that allows both qualitative and quantitative analyses and no additional BDDs are required. The efficiency of the four methods is compared using an example fault tree library. Copyright © 2008 John Wiley & Sons, Ltd.
Discrete sets of many‐body Sturmians
Authors: Randazzo J. M. , Frapiccini A. L. , Colavecchia F. D. , Gasaneo G. 
Published: August 2008

AbstractIn this work, we present a method to obtain two‐particle Coulomb Sturmians Functions (CSF) with an expansion in a set of L2 basis functions. In the two‐body case, we recover the exact (discrete) spectrum of the CSFs for negative energies and a discretized approximation for positive ones. Besides, we make use of this method to analyze the two‐independent electron problem as a Generalized Sturmian problem. We propose a discretized version of the wave function in terms of the CSF states, and show that the problem reduces to find numerical coincidences between energy‐dependent eigencharges of the mutually independent one‐electron systems. This expansion methodology includes the continuum information which is lost in the sets used previously in the literature, and is complete when the size of the basis goes to infinity. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
New approach for the correction of Ab initio molecular force fields in cartesian coordinates
Authors: Kochikov I. V. , Kuramshina G. M. , Stepanova A. V. 
Published: August 2008

AbstractThis paper presents a scaling technique applicable to molecular force constants in Cartesian coordinates. In the course of spectroscopic and structural research, it is a common practice to achieve better correspondence between measured and calculated vibrational frequencies of a molecule by appropriate scaling of the force constant matrices obtained by quantum chemical methods. However, the existing scaling procedure requires introduction of the complete system of internal coordinates, which may be tedious and time‐consuming for complex molecules. Scaling scheme suggested in this paper is applied directly to Cartesian force constant matrices and thus does not require introduction of the internal coordinates. Practical implementation of the proposed approach is illustrated with the examples of simple molecules. The scheme allows imposing special constraints on the determined Cartesian scale factors, which may be used for obtaining scale factors possessing transferability properties. These properties are very important for vibrational spectra calculations of related compounds, especially for large biological molecules, associates and nanostructures. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
Convergence of the binding energy of oxygen on Cu(100): A cautionary tale for computational chemists using periodic bound conditions
Authors: Bauschlicher Charles W. 
Published: August 2008

AbstractThe convergence of the binding energy of oxygen on Cu(100) as a function of the k‐points, energy cutoff for the inclusion of plane waves, surface model, and oxygen coverage is studied. Overall the convergence is good, with an accuracy of 0.1 eV obtained for an affordable level of treatment. Published 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009
Theoretical analysis of vibrational spectra and scaling‐factor of 2‐aryl‐1,3,4‐oxadiazole derivatives
Authors: Avci Davut , Atalay Yusuf 
Published: August 2008

AbstractIn this study, the direct molecular structure implementations for calculating vibrational spectra and scaling factors, and infrared intensities at both the Hartree–Fock (HF) and density functional (B3LYP) levels of theory with 6‐31G(d), 6‐311G(d), 6‐31++G(d,p), and 6‐311++G(d,p) basis sets are presented. Also, vibrational frequencies have been investigated as dependence on the choice of method and basis set. The parameters of molecular geometry and vibrational frequencies values of 2‐aryl‐1,3,4‐oxadiazoles 5a–g in the ground state have been calculated. Theoretical determination of vibrational frequencies is quite useful both in understanding the relationship between the molecular structures and scaling factor. The data of 2‐aryl‐1,3,4‐oxadiazoles 5a–g display significant electronic properties provide the basis for future design of efficient materials having the oxadiazole core and theoretical IR studies. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009