Comparative Protein Structure Modeling Using MODELLER

doi:10.1002/0471140864.PS0209S50

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Comparative Protein Structure Modeling Using MODELLER

Journal Article•DOI•

Comparative Protein Structure Modeling Using MODELLER

Narayanan Eswar¹, Ben Webb¹, Marc A. Marti-Renom, Mallur S. Madhusudhan¹, David Eramian¹, Min-Yi Shen¹, Ursula Pieper¹, Andrej Sali¹ - Show less +4 more•Institutions (1)

University of California, San Francisco¹

01 Nov 2007-Current protocols in protein science (Wiley-Blackwell)-Vol. 50, Iss: 1, pp 0-0

TL;DR: This unit describes how to calculate comparative models using the program MODELLER and discusses all four steps of comparative modeling, frequently observed errors, and some applications.

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Abstract: Functional characterization of a protein sequence is a common goal in biology, and is usually facilitated by having an accurate three-dimensional (3-D) structure of the studied protein. In the absence of an experimentally determined structure, comparative or homology modeling can sometimes provide a useful 3-D model for a protein that is related to at least one known protein structure. Comparative modeling predicts the 3-D structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described.

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Journal Article•DOI•

Comparative protein structure modeling using Modeller.

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Narayanan Eswar¹, Ben Webb¹, Marc A. Marti-Renom¹, Mallur S. Madhusudhan¹, David Eramian¹, Min-Yi Shen¹, Ursula Pieper¹, Andrej Sali¹ - Show less +4 more•Institutions (1)

University of California, San Francisco¹

01 Sep 2006-Current protocols in human genetics

TL;DR: This unit describes how to calculate comparative models using the program MODELLER and discusses all four steps of comparative modeling, frequently observed errors, and some applications.

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Abstract: Functional characterization of a protein sequence is one of the most frequent problems in biology. This task is usually facilitated by accurate three-dimensional (3-D) structure of the studied protein. In the absence of an experimentally determined structure, comparative or homology modeling can sometimes provide a useful 3-D model for a protein that is related to at least one known protein structure. Comparative modeling predicts the 3-D structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described.

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3,006 citations

Journal Article•DOI•

A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core

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Lukas Zimmermann¹, Andrew Stephens¹, Seung-Zin Nam¹, David Rau¹, Jonas M. Kübler¹, Marko Lozajic¹, Felix Gabler¹, Johannes Söding¹, Andrei N. Lupas¹, Vikram Alva¹ - Show less +6 more•Institutions (1)

Max Planck Society¹

01 Dec 2017-Journal of Molecular Biology

TL;DR: The new version of the MPI Bioinformatics Toolkit is introduced, focusing on improved features for the comprehensive analysis of proteins, as well as on promoting teaching.

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1,757 citations

Journal Article•DOI•

Pore-forming activity and structural autoinhibition of the gasdermin family

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Jingjin Ding¹, Kun Wang, Wang Liu, Yang She¹, Qi Sun, Jianjin Shi, Hanzi Sun, Da-Cheng Wang², Da-Cheng Wang¹, Feng Shao¹ - Show less +6 more•Institutions (2)

Chinese Academy of Sciences¹, Foshan University²

07 Jul 2016-Nature

TL;DR: It is demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis and provide insights into the roles of theGasdermin family in necrosis, immunity and diseases.

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Abstract: The N-terminal domains of gasdermin proteins cause pyroptotic cell death by oligomerizing to form membrane pores.

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1,567 citations

Journal Article•DOI•

ElliPro: a new structure-based tool for the prediction of antibody epitopes

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Julia Ponomarenko¹, Julia Ponomarenko², Huynh-Hoa Bui³, Wei Li, Nicholas Fusseder, Philip E. Bourne¹, Philip E. Bourne², Alessandro Sette⁴, Björn Peters⁴ - Show less +5 more•Institutions (4)

University of Montana¹, University of California, San Diego², Isis Pharmaceuticals³, La Jolla Institute for Allergy and Immunology⁴

02 Dec 2008-BMC Bioinformatics

TL;DR: ElliPro is a web-tool that implements Thornton's method for identifying continuous epitopes in the protein regions protruding from the protein's globular surface and, together with a residue clustering algorithm, the MODELLER program and the Jmol viewer, allows the prediction and visualization of antibody epitope in a given protein sequence or structure.

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Abstract: Background Reliable prediction of antibody, or B-cell, epitopes remains challenging yet highly desirable for the design of vaccines and immunodiagnostics. A correlation between antigenicity, solvent accessibility, and flexibility in proteins was demonstrated. Subsequently, Thornton and colleagues proposed a method for identifying continuous epitopes in the protein regions protruding from the protein's globular surface. The aim of this work was to implement that method as a web-tool and evaluate its performance on discontinuous epitopes known from the structures of antibody-protein complexes.

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988 citations

Cites methods from "Comparative Protein Structure Model..."

...Here we present ElliPro (derived from Ellipsoid and Protrusion), a web-tool that implements a modified version of Thornton's method [9] and, together with a residue clustering algorithm, the MODELLER program [10] and the Jmol viewer, allows the prediction and visualization of antibody epitopes in protein sequences and structures....
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...The user may change the threshold values for BLAST e-value and a number of templates that MODELLER uses as an input (Fig....
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...If a protein cannot be found in PDB that matches the BLAST criteria, MODELLER [10] is run to predict the protein 3D structure....
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...Results: Here we present ElliPro, a web-tool that implements Thornton's method and, together with a residue clustering algorithm, the MODELLER program and the Jmol viewer, allows the prediction and visualization of antibody epitopes in a given protein sequence or structure....
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Journal Article•DOI•

High resolution comparative modeling with RosettaCM

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Yifan Song¹, Frank DiMaio¹, Ray Yu-Ruei Wang¹, David E. Kim¹, Chris Miles¹, T. J. Brunette¹, James Thompson¹, David Baker², David Baker¹ - Show less +5 more•Institutions (2)

University of Washington¹, Howard Hughes Medical Institute²

08 Oct 2013-Structure

TL;DR: An improved method for comparative modeling, RosettaCM, which optimizes a physically realistic all-atom energy function over the conformational space defined by homologous structures, yields models with more accurate side-chain and backbone conformations than other methods.

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943 citations

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References

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Journal Article•DOI•

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

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Stephen F. Altschul¹, Thomas L. Madden, Alejandro A. Schäffer¹, Jinghui Zhang, Zheng Zhang², Webb Miller², David J. Lipman - Show less +3 more•Institutions (2)

National Institutes of Health¹, Pennsylvania State University²

01 Sep 1997-Nucleic Acids Research

TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.

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Abstract: The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

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70,111 citations

Journal Article•DOI•

Clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice

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Julie D. Thompson, Desmond G. Higgins, Toby J. Gibson

11 Nov 1994-Nucleic Acids Research

TL;DR: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved and modifications are incorporated into a new program, CLUSTAL W, which is freely available.

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Abstract: The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.

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63,427 citations

Journal Article•DOI•

MUSCLE: multiple sequence alignment with high accuracy and high throughput

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Robert C. Edgar

01 Mar 2004-Nucleic Acids Research

TL;DR: MUSCLE is a new computer program for creating multiple alignments of protein sequences that includes fast distance estimation using kmer counting, progressive alignment using a new profile function the authors call the log-expectation score, and refinement using tree-dependent restricted partitioning.

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Abstract: We describe MUSCLE, a new computer program for creating multiple alignments of protein sequences. Elements of the algorithm include fast distance estimation using kmer counting, progressive alignment using a new profile function we call the logexpectation score, and refinement using treedependent restricted partitioning. The speed and accuracy of MUSCLE are compared with T-Coffee, MAFFT and CLUSTALW on four test sets of reference alignments: BAliBASE, SABmark, SMART and a new benchmark, PREFAB. MUSCLE achieves the highest, or joint highest, rank in accuracy on each of these sets. Without refinement, MUSCLE achieves average accuracy statistically indistinguishable from T-Coffee and MAFFT, and is the fastest of the tested methods for large numbers of sequences, aligning 5000 sequences of average length 350 in 7 min on a current desktop computer. The MUSCLE program, source code and PREFAB test data are freely available at http://www.drive5. com/muscle.

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37,524 citations

Additional excerpts

...Sequence- and structure-based sequence alignment AlignMe (Khafizov et al., 2010) http://www.bioinfo.mpg.de/AlignMe/ CLUSTALW (Thompson et al., 1994) http://www2.ebi.ac.uk/clustalw/ COMPASS (Sadreyev and Grishin, 2003) ftp://iole.swmed.edu/pub/compass/ EXPRESSO (Armougom et al., 2006) http://igs-server.cnrsmrs.fr/Tcoffee/tcoffee_cgi/index.cgi FastA (Pearson, 2000) http://www.ebi.ac.uk/Tools/sss/fasta/ FFAS03 (Jaroszewski et al., 2005) http://ffas.burnham.org/ FUGUE (Shi et al., 2001) http://www-cryst.bioc.cam.ac.uk/fugue GENTHREADER (Jones, 1999; McGuffin and Jones, 2003) http://bioinf.cs.ucl.ac.uk/psipred/ continued Modeling Structure from Sequence 5.6.3 Current Protocols in Bioinformatics Supplement 47 HHBlits/HHsearch (Remmert et al., 2012) http://toolkit.lmb.uni-muenchen.de/hhsuite MAFFT (Katoh and Standley, 2013) http://mafft.cbrc.jp/alignment/software/ MUSCLE (Edgar, 2004) http://www.drive5.com/muscle MUSTER (Wu and Zhang, 2008) http://zhanglab.ccmb.med.umich.edu/ MUSTER PROMALS3D (Pei et al., 2008) http://prodata.swmed.edu/promals3d/ promals3d.php PSI-BLAST (Altschul et al., 1997) http://blast.ncbi.nlm.nih.gov/Blast.cgi PSIPRED (McGuffin et al., 2000) http://bioinf.cs.ucl.ac.uk/psipred/ SALIGN (Eswar et al., 2003) http://www.salilab.org/salign/ SAM-T08 (Karplus et al., 2003; Karplus, 2009) http://compbio.soe.ucsc.edu/HMM-apps/ Staccato (Shatsky et al., 2006) http://bioinfo3d.cs.tau.ac.il/staccato/ T-Coffee (Notredame, 2010; also see UNIT 3.8) http://www.tcoffee.org/...
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...…(Remmert et al., 2012) http://toolkit.lmb.uni-muenchen.de/hhsuite MAFFT (Katoh and Standley, 2013) http://mafft.cbrc.jp/alignment/software/ MUSCLE (Edgar, 2004) http://www.drive5.com/muscle MUSTER (Wu and Zhang, 2008) http://zhanglab.ccmb.med.umich.edu/ MUSTER PROMALS3D (Pei et al., 2008)…...
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Journal Article•DOI•

The Protein Data Bank

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Helen M. Berman¹, John D. Westbrook, Zukang Feng, Gary L. Gilliland, Talapady N. Bhat, Helge Weissig, Ilya N. Shindyalov, Philip E. Bourne - Show less +4 more•Institutions (1)

Rutgers University¹

01 Jan 2000-Nucleic Acids Research

TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.

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Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.

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34,239 citations

Additional excerpts

...ModBase (Pieper et al., 2011) http://www.salilab.org/modbase/ PDB (Berman et al., 2000) http://www.pdb.org/ Protein Model Portal (Arnold et al., 2009; Haas et al., 2013) http://www.proteinmodelportal.org/ SwissModel Repository (Kiefer et al., 2009) http://swissmodel.expasy.org/repository/...
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Journal Article•DOI•

PROCHECK: a program to check the stereochemical quality of protein structures

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Roman A. Laskowski, Malcolm W. MacArthur, David S. Moss, Janet M. Thornton

01 Apr 1993-Journal of Applied Crystallography

TL;DR: The PROCHECK suite of programs as mentioned in this paper provides a detailed check on the stereochemistry of a protein structure and provides an assessment of the overall quality of the structure as compared with well refined structures of the same resolution.

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Abstract: The PROCHECK suite of programs provides a detailed check on the stereochemistry of a protein structure Its outputs comprise a number of plots in PostScript format and a comprehensive residue-by-residue listing These give an assessment of the overall quality of the structure as compared with well refined structures of the same resolution and also highlight regions that may need further investigation The PROCHECK programs are useful for assessing the quality not only of protein structures in the process of being solved but also of existing structures and of those being modelled on known structures

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22,829 citations

Additional excerpts

...…1993) http://nihserver.mbi.ucla.edu/ERRAT/ ModEval http://salilab.org/modeval/ ProQ2 (Ray et al., 2012) http://proq2.theophys.kth.se/ PROCHECK (Laskowski et al., 1993) http://www.ebi.ac.uk/thorntonsrv/software/PROCHECK/ Prosa2003 (Sippl, 1993; Wiederstein and Sippl,…...
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...ANOLEA (Melo and Feytmans, 1998) http://melolab.org/anolea/index.html ERRAT (Colovos and Yeates, 1993) http://nihserver.mbi.ucla.edu/ERRAT/ ModEval http://salilab.org/modeval/ ProQ2 (Ray et al., 2012) http://proq2.theophys.kth.se/ PROCHECK (Laskowski et al., 1993) http://www.ebi.ac.uk/thorntonsrv/software/PROCHECK/ Prosa2003 (Sippl, 1993; Wiederstein and Sippl, 2007) http://www.came.sbg.ac.at QMEAN local (Benkert et al., 2011) http://www.openstructure.org/download/ SwissModel Workspace (Arnold et al., 2006) http://swissmodel.expasy.org/workspace/index .php?func=tools_structureassessment1 VERIFY3D (Luthy et al., 1992) http://www.doembi.ucla.edu/Services/Verify_3D/ WHATCHECK (Hooft et al., 1996) http://www.cmbi.kun.nl/gv/whatcheck/...
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