3,249 research outputs found

    Conservation and specialization in PAS domain dynamics

    Get PDF
    The PAS (Per-ARNT-Sim) superfamily is presented as a well-suited study case to demonstrate how comparison of functional motions among distant homologous proteins with conserved fold characteristics may give insight into their functional specialization. Based on the importance of structural flexibility of the receptive structures in anticipating the signal-induced conformational changes of these sensory systems, the dynamics of these structures were analysed. Molecular dynamics was proved to be an effective method to obtain a reliable picture of the dynamics of the crystal structures of HERG, phy3, PYP and FixL, provided that an extensive conformational space sampling is performed. Other reliable sources of dynamic information were the ensembles of NMR structures of hPASK, HIF-2α and PYP. Essential dynamics analysis was successfully employed to extract the relevant information from the sampled conformational spaces. Comparison of motion patterns in the essential subspaces, based on the structural alignment, allowed identification of the specialized region in each domain. This appears to be evolved in the superfamily by following a specific trend, that also suggests the presence of a limited number of general solutions adopted by the PAS domains to sense external signals. These findings may give insight into unknown mechanisms of PAS domains and guide further experimental studies. © The Author 2005. Published by Oxford University Press. All rights reserved

    Predicting the accuracy of protein-ligand docking on homology models

    Get PDF
    Ligand-protein docking is increasingly used in Drug Discovery. The initial limitations imposed by a reduced availability of target protein structures have been overcome by the use of theoretical models, especially those derived by homology modeling techniques. While this greatly extended the use of docking simulations, it also introduced the need for general and robust criteria to estimate the reliability of docking results given the model quality. To this end, a large-scale experiment was performed on a diverse set including experimental structures and homology models for a group of representative ligand-protein complexes. A wide spectrum of model quality was sampled using templates at different evolutionary distances and different strategies for target-template alignment and modeling. The obtained models were scored by a selection of the most used model quality indices. The binding geometries were generated using AutoDock, one of the most common docking programs. An important result of this study is that indeed quantitative and robust correlations exist between the accuracy of docking results and the model quality, especially in the binding site. Moreover, state-of-the-art indices for model quality assessment are already an effective tool for an a priori prediction of the accuracy of docking experiments in the context of groups of proteins with conserved structural characteristics.Contract/grant sponsor: National Institutes of Health; contract/grant numbers: ES00768

    Structural alphabets derived from attractors in conformational space

    Get PDF
    Background: The hierarchical and partially redundant nature of protein structures justifies the definition of frequently occurring conformations of short fragments as 'states'. Collections of selected representatives for these states define Structural Alphabets, describing the most typical local conformations within protein structures. These alphabets form a bridge between the string-oriented methods of sequence analysis and the coordinate-oriented methods of protein structure analysis.Results: A Structural Alphabet has been derived by clustering all four-residue fragments of a high-resolution subset of the protein data bank and extracting the high-density states as representative conformational states. Each fragment is uniquely defined by a set of three independent angles corresponding to its degrees of freedom, capturing in simple and intuitive terms the properties of the conformational space. The fragments of the Structural Alphabet are equivalent to the conformational attractors and therefore yield a most informative encoding of proteins. Proteins can be reconstructed within the experimental uncertainty in structure determination and ensembles of structures can be encoded with accuracy and robustness.Conclusions: The density-based Structural Alphabet provides a novel tool to describe local conformations and it is specifically suitable for application in studies of protein dynamics. © 2010 Pandini et al; licensee BioMed Central Ltd

    GSATools: Analysis of allosteric communication and functional local motions using a structural alphabet

    Get PDF
    Motivation: GSATools is a free software package to analyze conformational ensembles and to detect functional motions in proteins by means of a structural alphabet. The software integrates with the widely used GROMACS simulation package and can generate a range of graphical outputs. Three applications can be supported: (i) investigation of the conformational variability of local structures; (ii) detection of allosteric communication; and (iii) identification of local regions that are critical for global functional motions. These analyses provide insights into the dynamics of proteins and allow for targeted design of functional mutants in theoretical and experimental studies. Availability: The C source code of the GSATools, along with a set of pre-compiled binaries, is freely available under GNU General Public License from http://mathbio.nimr.mrc.ac.uk/wiki/GSATools. Contact: alessandro.pandini@kcl. ac.uk or [email protected] Supplementary information: Supplementary data are available at Bioinformatics online. © 2013 The Author 2013. Published by Oxford University Press

    Applications Soil Observation in the Field PT. Anugerah Sumber Makmur Minamas Research Center

    Get PDF
    Many employees still have difficulty in entering data and searching for appropriate data. Employees who still input data manually and it takes a long time. The existence of a soil observation application in the field of PT. Anugrah Sumber Makmur Minamas Research Center was created with the aim of assisting employees in entering data and searching for data quickly and accurately. This application is made using the PHP programming language and MySQL as the database. The system development method in making this application uses the design sprint method. Based on tests conducted on users, this application functionally runs as expected and the success rate is 92%

    Exploiting the WH/ZH symmetry in the search for New Physics

    Full text link
    We suggest to isolate the loop-induced gluon-initiated component (gg→ZHgg\to ZH) for associated ZHZH production by using the similarity of the Drell-Yan-like component for ZHZH production to the WHWH process. We argue that the cross-section ratio of the latter two processes can be predicted with high theoretical accuracy. Comparing it to the experimental ZH/WHZH/WH cross-section ratio should allow to probe for New Physics in the gg→ZHgg\to ZH component at the HL-LHC. We consider typical BSM scenarios in order to exemplify the effect they would have on the proposed observable.Comment: 22 pages, 10 figures. v2: Minor changes; matches published versio

    Structural and functional characterization of the aryl hydrocarbon receptor ligand binding domain by homology modeling and mutational analysis

    Get PDF
    The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that is activated by a structurally diverse array of synthetic and natural chemicals, including toxic halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Analysis of the occurring in the AhR ligand binding and activation processes requires structural information on the AhR Per-Arnt-Sim (PAS) B-containing ligand binding domain, for which no experimentally determined structure has been reported. With the availability of extensive structural information on homologous PAS-containing proteins, a reliable model of the mouse AhR PAS B domain was developed by comparative modeling techniques. The PAS domain structures of the functionally related hypoxia-inducible factor 2α (HIF-2α) and AhR nuclear translocator (ARNT) proteins, which exhibit the highest degree of sequence identity and similarity with AhR, were chosen to develop a two-template model. To confirm the features of the modeled domain, the effects of point mutations in selected residue positions on both TCDD binding to the AhR and TCDD-dependent transformation and DNA binding were analyzed. Mutagenesis and functional analysis results are consistent with the proposed model and confirm that the cavity modeled in the interior of the domain is indeed involved in ligand binding. Moreover, the physicochemical characteristics of some residues and of their mutants, along with the effects of mutagenesis on TCDD and DNA binding, also suggest some key features that are required for ligand binding and activation of mAhR at a molecular level, thus providing a framework for further studies. © 2007 American Chemical Society

    Detection of the TCDD binding-fingerprint within the Ah receptor ligand binding domain by structurally driven mutagenesis and functional analysis

    Get PDF
    The aryl hydrocarbon receptor (AhR) is a ligand-dependent, basic helix-loop-helix Per-Arnt-Sim (PAS)-containing transcription factor that can bind and be activated by structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Our previous three-dimensional homology model of the mouse AhR (mAhR) PAS B ligand binding domain allowed identification of the binding site and its experimental validation. We have extended this analysis by conducting comparative structural modeling studies of the ligand binding domains of six additional highaffinity mammalian AhRs. These results, coupled with site-directed mutagenesis and AhR functional analysis, have allowed detection of the "TCDD binding-fingerprint" of conserved residues within the ligand binding cavity necessary for high-affinity TCDD binding and TCDD-dependent AhR transformation DNA binding. The essential role of selected residues was further evaluated using molecular docking simulations of TCDD with both wild-type and mutant mAhRs. Taken together, our results dramatically improve our understanding of the molecular determinants of TCDD binding and provide a basis for future studies directed toward rationalizing the observed species differences in AhR sensitivity to TCDD and understanding the mechanistic basis for the dramatic diversity in AhR ligand structure. © 2009 American Chemical Society

    Detecting similarities among distant homologous proteins by comparison of domain flexibilities

    Get PDF
    Aim of this work is to assess the informativeness of protein dynamics in the detection of similarities among distant homologous proteins. To this end, an approach to perform large-scale comparisons of protein domain flexibilities is proposed. CONCOORD is confirmed as a reliable method for fast conformational sampling. The root mean square fluctuation of alpha carbon positions in the essential dynamics subspace is employed as a measure of local flexibility and a synthetic index of similarity is presented. The dynamics of a large collection of protein domains from ASTRAL/SCOP40 is analyzed and the possibility to identify relationships, at both the family and the superfamily levels, on the basis of the dynamical features is discussed. The obtained picture is in agreement with the SCOP classification, and furthermore suggests the presence of a distinguishable familiar trend in the flexibility profiles. The results support the complementarity of the dynamical and the structural information, suggesting that information from dynamics analysis can arise from functional similarities, often partially hidden by a static comparison. On the basis of this first test, flexibility annotation can be expected to help in automatically detecting functional similarities otherwise unrecoverable. © 2007 The Author(s)

    HUBUNGAN ANTARA VALS (VALUE AND LIFESTYLE) DENGAN STYLE FASHION MUSLIM KONTEMPORER TIPE CLASSIC ELEGANT PADA KONSUMEN MEREK X

    Get PDF
    Penelitian ini didasari oleh berkembang pesatnya industri fashion muslim di Indonesia yang juga diiringi dengan meningkatnya persaingan antara para pelaku industri fashion muslim tersebut. Tujuan yang ingin dicapai dalam penelitian ini adalah untuk mengetahui seberapa besar hubungan antara VALS (value and lifestyle) dengan style fashion muslim kontemporer tipe classic elegant pada konsumen merek X. Penelitian ini menggunakan pendekatan kuantitatif dengan metode korelasional. Pengambilan sampel dalam penelitian ini menggunakan teknik simple random sampling. Subjek pada penelitian ini adalah 147 konsumen merek X. Instrumen yang digunakan yaitu instrumen VALS dan style fashion muslim kontemporer tipe classic elegant. Instrumen VALS diadaptasi dari The US VALSTM Survey milik Strategic Business Insights (SBI), sedangkan instrumen style fashion muslim kontemporer tipe classic elegant disusun sendiri oleh peneliti. Analisis data dilakukan dengan menggunakan korelasi Rank Spearman. Hasil penelitian menunjukkan (1) tipe VALS pada konsumen merek X didominasi oleh tipe believers (2) tidak terdapat hubungan yang signifikan antara tipe VALS thinkers, experiencers, achievers, believers, makers, strivers, survivors, dan innovators dengan tipe style fashion muslim kontemporer tipe classic elegant pada konsumen merek X.---------This research is based on the rapid growth of moeslim’s industrial fashion in Indonesia which is also accompanied by the increase of competition between the moeslim’s fashion industries themselves. The purpose in this research is to perceive how many the relation between VALS (value and lifestyle) with moeslim’s contemporary fashion style on brand X consumers. This research uses quantitative approach with correlation method. The sampling in this research uses simple random sampling technique. The subjects in this research are 147 brand X consumers. The instruments that are used are VALS instruments and contemporary moeslim’s fashion style classic elegant type. VALS instruments are adapted from The US VALSTM Survey by Strategic Business Insights (SBI), while the instruments of moeslim’s contemporary fashion style classic elegant type’s instruments are composed by the researcher. The data analysis is done by Rank Spearman’s correlation. The result of this research shows that (1) VALS types on brand X consumers is dominated by believer types (2) there are no significant relationship between VALS thinkers, experiencers, achievers, believers, makers, strivers, survivors, and innovators with moeslim’s contemporary fashion style classic elegant types on brand X consumers
    • 

    corecore