ArticlePDF Available

Friend, an integrated analytical front-end application for bioinformatics

October 2005
Bioinformatics 21(18):3677-8

DOI:10.1093/bioinformatics/bti602

Source
PubMed

Authors:

Alexej Abyzov

Mayo Clinic - Rochester

Chesley Leslin

Northeastern University

Unlabelled: Friend is a bioinformatics application designed for simultaneous analysis and visualization of multiple structures and sequences of proteins and/or DNA/RNA. The application provides basic functionalities, such as structure visualization, with different rendering and coloring, sequence alignment and simple phylogeny analysis, along with a number of extended features to perform more complex analyses of sequence structure relationships, including structural alignment of proteins, investigation of specific interaction motifs, studies of protein-protein and protein-DNA interactions and protein super-families. It is also useful for functional annotation of proteins, protein modeling and protein folding studies. Friend provides three levels of usage: (1) an extensive GUI for a scientist with no programming experience, (2) a command line interface for scripting for a scientist with some programming experience and (3) the ability to extend Friend with user written libraries for an experienced programmer. The application is linked and communicates with local and remote sequence and structure databases. Availability: http://mozart.bio.neu.edu/friend.

Friend displays structures, sequences and phylogeny tree for 137 lysozymes.

…

Figures - uploaded by Chesley Leslin

Content may be subject to copyright.

Content uploaded by Chesley Leslin

Content may be subject to copyright.

BIOINFORMATICS

Friend, an Integrated Analytical Front-end Application for Bioin-

formatics

Alexej Abyzov, Mounir Errami, Chesley M. Leslin, and Valentin A. Ilyin

Department of Biology, Northeastern University, Boston, Massachusetts, USA

Received on ; revised on ; accepted on

Advance Access publication . . .

ABSTRACT

Friend is a bioinformatics application designed for simultaneous

analysis and visualization of multiple structures and sequences of

proteins and/or DNA/RNA. The application provides basic function-

alities such as: structure visualization with different rendering and

coloring, sequence alignment, and simple phylogeny analysis,

along with a number of extended features to perform more complex

analyses of sequence structure relationships, including: structural

alignment of proteins, investigation of specific interaction motifs,

studies of protein-protein and protein-DNA interactions, and protein

super-families. It is also useful for functional annotation of proteins,

protein modeling, and protein folding studies. Friend provides three

levels of usage; 1) an extensive GUI for a scientist with no pro-

gramming experience, 2) a command line interface for scripting for a

scientist with some programming experience, and 3) the ability to

extend Friend with user written libraries for an experienced pro-

grammer. The application is linked and communicates with local and

remote sequence and structure databases.

Availability: http://mozart.bio.neu.edu/friend

Contact: ilyin@neu.edu, abyzov@mozart.bio.neu.edu

Many areas of research in biology, biomedicine and bio-

informatics require tools to perform comparative analytical studies

of DNA and protein sequence and structure families. There are

numerous examples where sequence-structure function research is

essential, including the analysis of conservative positions, active

and binding site residues, variations in orthologous and paralogous

sequences and structures, sequence alignments, structural align-

ments and classification, identification of the key residues for pro-

tein functionality and formation of macromolecular complexes,

phylogenetic tree analysis, and simple visual inspection. Therefore,

extended applications which integrate data from different sources,

facilitate in visualization and assist in analytical studies are an

everyday need in biological, biochemical, molecular biology and

related research areas.

Integration of different types of data is challenging and

not always straightforward. Despite the significant variety of ap-

plications in each particular research area: sequence analysis, struc-

ture studies, and phylogeny only a few such applications integrate

the data, for example JalView (Clamp et al., 2004), Cn3D (Wang

et al., 2000), Pfaat (Johnson et al., 2003), DeepView (Schwede et

To whom correspondence should be addressed, ilyin@neu.edu.

al., 2003). One more example of such an attempt to integrate se-

quence and structure analysis, ModView, a Netscape plug-in, has

been recently reported (Ilyin et al., 2003). While the integrative

analytical ability of the application has been found useful for pro-

teins analysis and the plug-in is downloaded constantly by

Linux/Netscape version 4 users, ModView has a clear downside

because of the strong dependence on the evolution of the Netscape

browser, in particular, Netscape does not provide backward com-

patibilities in its new versions and has restricted data handling

abilities. To avoid dependence on any third party software a new

stand-alone program, Friend, has been developed which itself

communicates with internet resources, provides data integration

between structure and sequence modules and local user files (see

Figure 1). The majority of ModView’s functionalities have been

re-implemented in Friend, while many new options have been

added including a user’s ability to extend Friend with new func-

tionality with dynamic libraries, i.e. its own plug-ins.

Figure 1. General architecture of Friend.

Friend is a stand-alone, multi-module, web-related appli-

cation, designed to be a front-end user interface for visual and

analytical studies on multiple sequences and multiple structures in

real time on a personal computer (see Figure 2). Both structure

and sequence data are linked to local and remote databases provid-

ing researchers with a comprehensive picture about related pro-

teins. Friend allows a user to visualize and manipulate hundreds of

spatial protein or DNA/RNA structures and sequences, and pro-

vides an easy to use interface.

There are more than 200 basic commands, including

various coloring and rendering of the protein structure, exhaustive

selection of subsets of atoms, residues, stereoviewing of structures,

C++

Structure

Module

Java

Sequence

Module

C++main

J-main

JSQL

C plugin

J plugin

Text

bio

DBs

SQL

bio

DBs

Bio

Informatics

Applications

Bridge

Linux/Unix

Windows

Mac

Friend

Bioinformatics Advance Access published August 2, 2005

by guest on August 22, 2015http://bioinformatics.oxfordjournals.org/Downloaded from

A. Abyzov et al.

interactive atom/residue identification and labeling, alignment

editing, phylogeny clustering and tree viewing, pairwise sequence

alignment, cross coloring of sequence and structures, changing

residue representation in structure by simply clicking on it in the

sequence, saving the results in a variety of text and graphical for-

mats, and producing publication quality pictures. Several popular

alignment and structure representation formats are supported, in-

cluding: PDB, FASTA, PIR, CLUSTAL, and SKY. The SKY-

format was created to fulfill the demand for saving and linking

sequence and structure data cooperatively.

Figure 2. Friend displays structures, sequences and phylogeny tree for 137

lysozymes.

The advantage of Friend is the three levels of its usage:

1) for a scientist with no programming experience, Friend provides

users with an extensive GUI (the description can be found in the

program manual); 2) for a scientist with some programming ex-

perience, it provides the possibility to create user-defined menus in

a XML-file in order to use and combine any of the more than 200

commands; and 3) for a programmer, the ability to extend Friend

with user written libraries. This is accomplished by use of abstract

classes, providing functions to access and manipulate internal ap-

plication data. Using the abstract interfaces one can write code and

compile it into a dynamically loaded library, which is loaded and

executed during run time. The absence or presence of the library

does not affect the functionality of the Friend core. The opportu-

nity to add user written libraries allows users to perform more

complex and specific analysis of the studied object in a time effec-

tive manner, since there is no need to develop basic routine func-

tions; this also ensures that the code developed by different people

does not interfere with each other. As an example, the TOPOFIT

method for the structural alignment of proteins (Ilyin et al., 2004)

has been implemented as a separate dynamically loaded library.

Another powerful feature of the Friend application is the

ability to provide an interface to various sequence and structure

databases and other bioinformatics applications. Friend is used as a

visual front-end interface to the Structural Exon Database, SEDB

(Leslin et al., 2004) and to a database for mapping non-

synonymous SNPs, StSNP (Uzun et al., 2004). Internal integrated

client modules allow a user to perform similarity searches using

BLAST and to load protein structures from the PDB on “the fly”.

Friend also provides an interface to the homology modeling soft-

ware MODELLER (Sali and Blundell, 1993) and to the multiple

sequence alignment program ClustalW (Jeanmougin et al., 1998).

The QHULL (Barber, 1996) library for fast Delaunay Tessellation

(Delaunay, 1934) is integrated in Friend to analyze protein and

DNA/RNA atom-atom, residues-residue, residues-base, base-base

interactions along with the visualization of the tessellation in dif-

ferent views.

Friend is an ongoing project; future directions include

development of several additional modules to broaden the number

of databases interfaces (to NCBI databases, SWISS-PROT, Uni-

Prot, etc); porting it to the Mac OS and supplying the application

as a plug-in for a number of popular browsers (Internet Explorer,

Netscape, Mozilla, and FireFox). Friend has extensively used in a

Bioinformatics course and has a constant rate of outside installa-

tions ~25-30 per month since January, 2003.

REFERENCES

Barber, C. B. Dobkin D. P. and Huhdanpaa H. T. The Quickhull algorithm for convex

hulls. ACM Trans.on Mathematical Software 22(4):469-483. 1996.

http://www.qhull.org

Clamp,M., Cuff, J., Searle, S. M. and Barton, G. J. (2004). The Jalview Java Align-

ment Editor. Bioinformatics 20, 426-427.

Delaunay,B. (1934). Sur La Sphere Vide. Bull Acad Science USSR VII: Class Sci

Mat Nat 793-800.

Ilyin,V.A., Abyzov, A. and Leslin, C. M. (2004). Structural Alignment of Proteins by

a Novel TOPOFIT Method, As a Superimposition of Common Volumes at a

Topomax Point. Protein Sci 13, 1865-1874.

Jeanmougin,F., Thompson, J. D., Gouy, M., Higgins, D. G. and Gibson, T. J. (1998).

Multiple Sequence Alignment With Clustal X. Trends Biochem Sci 23, 403-405.

Johnson,J.M., Mason, K., Moallemi, C., Xi, H., Somaroo, S. and Huang, E. S. (2003).

Protein Family Annotation in a Multiple Alignment Viewer. Bioinformatics 19,

544-545.

Leslin,C.M., Abyzov, A. and Ilyin, V. A. (2004). Structural Exon Database, SEDB,

Mapping Exon Boundaries on Multiple Protein Structures. Bioinformatics.

Sali,A. and Blundell, T. L. (1993). Comparative Protein Modelling by Satisfaction of

Spatial Restraints. J Mol Biol 234, 779-815.

Schwede,T., Kopp, J., Guex, N. and Peitsch, M. C. (2003). SWISS-MODEL: An

Automated Protein Homology-Modeling Server. Nucleic Acids Res 31, 3381-

3385.

Uzun, A., Leslin, C., and Ilyin, V. A. StSNP:Structure SNP, a database for mapping

nonsnynonymous SNPs onto spatial structures of proteins. ASBMB Annual Meet-

ing and 8th IUBMB Conference. 12-6-2004.

Wang,Y., Geer, L. Y., Chappey, C., Kans, J. A. and Bryant, S. H. (2000). Cn3D:

Sequence and Structure Views for Entrez. Trends Biochem Sci 25, 300-302.

by guest on August 22, 2015http://bioinformatics.oxfordjournals.org/Downloaded from

IBiSS, a versatile and interactive tool for integrated sequence and 3D structure analysis of large macromolecular complexes

Article

Jun 2015
BIOINFORMATICS

MotivationIn the past few years, an increasing number of crystal and cryo electron microscopy (cryo-EM) structures of large macromolecular complexes, such as the ribosome or the RNA polymerase, have become available from various species. These multi-subunit complexes can be difficult to analyse at the level of amino acid sequence in combination with the 3D structural organization of the complex. Therefore, novel tools for simultaneous analysis of structure and sequence information of complex assemblies are required to better understand the basis of molecular mechanisms and their functional implications.ResultsHere, we present a web-based tool, IBiSS (Integrative Biology of Sequences and Structures), which is designed for interactively displaying 3D structures and selected sequences of subunits from large macromolecular complexes thus allowing simultaneous structure-sequence analysis such as conserved residues involved in catalysis or protein-protein interfaces. This tool comprises a Graphic User Interface (GUI) and uses a rapid-access internal database, containing the relevant pre-aligned multiple sequences across all species available and 3D structural information. These annotations are automatically retrieved and updated from UniProt and crystallographic and cryo-EM data available in the Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB).Availability and ImplementationThe database contains all currently available structures of ribosomes, RNA polymerases, nucleosomes, proteasome, photosystem I and II complexes. IBiSS is available at http://ibiss.igbmc.frContact:klaholz@igbmc.fr. © The Author (2015). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

SUMOylation in Giardia lamblia: A Conserved Post-Translational Modification in One of the Earliest Divergent Eukaryotes

Article

Full-text available

Jul 2012

Post-translational modifications are able to regulate protein function and cellular processes in a rapid and reversible way. SUMOylation, the post-translational modification of proteins by the addition of SUMO, is a highly conserved process that seems to be present in modern cells. However, the mechanism of protein SUMOylation in earlier divergent eukaryotes, such as Giardia lamblia, is only starting to become apparent. In this work, we report the presence of a single SUMO gene encoding to SUMO protein in Giardia. Monoclonal antibodies against recombinant Giardia SUMO protein revealed the cytoplasmic localization of native SUMO in wild-type trophozoites. Moreover, the over-expression of SUMO protein showed a mainly cytoplasmic localization, though also neighboring the plasma membrane, flagella, and around and even inside the nuclei. Western blot assays revealed a number of SUMOylated proteins in a range between 20 and 120 kDa. The genes corresponding to putative enzymes involved in the SUMOylation pathway were also explored. Our results as a whole suggest that SUMOylation is a process conserved in the eukaryotic lineage, and that its study is significant for understanding the biology of this interesting parasite and the role of post-translational modification in its evolution.

Program Comprehension Using Aspects

Article

Full-text available

Aspect Oriented Programming (AOP) is a powerful re- ective programming tool. In this paper we discuss how simple yet effective AOP constructs can be used to facilitate the process of program comprehension on three bodies of code. The r st is the Java portion of a sizable third party legacy system for manipulating and displaying protein se- quences entitled Friend. The second is Eclipse, an open source Java IDE. The third is Compress, a SPEC JVM98 Java benchmark. We study uses of the AspectJ AOP lan- guage to expose both dynamic and static software charac- teristics. Examples provided are actual code and data from our experience re-engineering the Friend software but the AOP techniques presented can be applied towards any sys- tem.

Skipping of Exons by Premature Termination of Transcription and Alternative Splicing within Intron-5 of the Sheep SCF Gene: A Novel Splice Variant

Article

Full-text available

Jun 2012
PLOS ONE

Stem cell factor (SCF) is a growth factor, essential for haemopoiesis, mast cell development and melanogenesis. In the hematopoietic microenvironment (HM), SCF is produced either as a membrane-bound (-) or soluble (+) forms. Skin expression of SCF stimulates melanocyte migration, proliferation, differentiation, and survival. We report for the first time, a novel mRNA splice variant of SCF from the skin of white merino sheep via cloning and sequencing. Reverse transcriptase (RT)-PCR and molecular prediction revealed two different cDNA products of SCF. Full-length cDNA libraries were enriched by the method of rapid amplification of cDNA ends (RACE-PCR). Nucleotide sequencing and molecular prediction revealed that the primary 1519 base pair (bp) cDNA encodes a precursor protein of 274 amino acids (aa), commonly known as 'soluble' isoform. In contrast, the shorter (835 and/or 725 bp) cDNA was found to be a 'novel' mRNA splice variant. It contains an open reading frame (ORF) corresponding to a truncated protein of 181 aa (vs 245 aa) with an unique C-terminus lacking the primary proteolytic segment (28 aa) right after the D(175)G site which is necessary to produce 'soluble' form of SCF. This alternative splice (AS) variant was explained by the complete nucleotide sequencing of splice junction covering exon 5-intron (5)-exon 6 (948 bp) with a premature termination codon (PTC) whereby exons 6 to 9/10 are skipped (Cassette Exon, CE 6-9/10). We also demonstrated that the Northern blot analysis at transcript level is mediated via an intron-5 splicing event. Our data refine the structure of SCF gene; clarify the presence (+) and/or absence (-) of primary proteolytic-cleavage site specific SCF splice variants. This work provides a basis for understanding the functional role and regulation of SCF in hair follicle melanogenesis in sheep beyond what was known in mice, humans and other mammals.

On the unyielding hydrophobic core of villin headpiece

Article

May 2012
PROTEIN SCI

Villin headpiece (HP67) is a small, autonomously-folding domain that has become a model system for understanding the fundamental tenets governing protein folding. In this communication, we explore the role that Leu61 plays in the structure and stability of the construct. Deletion of Leu61 results in a completely unfolded protein that cannot be expressed in Escherichia coli. Omission of only the aliphatic leucine side chain (HP67 L61G) perturbed neither the backbone conformation nor the orientation of local hydrophobic side chains. As a result, a large, solvent-exposed hydrophobic pocket, a negative replica of the leucine side-chain, was created on the surface. The loss of the hydrophobic interface between leucine 61 and the hydrophobic pocket destabilized the construct by ~3.3 kcal/mol. Insertion of a single glycine residue immediately before Leu61 (HP67 L61[GL]) was also highly destabilizing and had the effect of altering the backbone conformation (α-helix to π-helix) in order to precisely preserve the wild-type position and conformation of all hydrophobic residues, including Leu61. In addition to demonstrating that the hydrophobic side-chain of Leu61 is critically important for the stability of villin headpiece, our results are consistent with the notion that the precise interactions present within the hydrophobic core, rather than the hydrogen bonds that define the secondary structure, specify a protein's fold.

Sequence alignment: Methods, models, concepts, and strategies

Article

Mar 2009

M.S. Rosenberg

The sequencing of the human genome involved thousands of scientists but used relatively few tools. Today, obtaining sequences is simpler, but aligning the sequences-making sure that sequences from one source are properly compared to those from other sources-remains a complicated but underappreciated aspect of comparative molecular biology. This volume, the first to focus on this crucial step in analyzing sequence data, is about the practice of alignment, the procedures by which alignments are established, and more importantly, how the outcomes of any alignment algorithm should be interpreted. Edited by Michael S. Rosenberg with essays by many of the field's leading experts, Sequence Alignment covers molecular causes, computational advances, approaches for assessing alignment quality, and philosophical underpinnings of the algorithms themselves.

Pediatric Pathology In The Year 2050

Article

Jul 2015

Don B Singer

The study of pathology in fetuses, infants, and children had its beginnings in the mid-19th century. One hundred and sixty-five years later, hundreds of pediatric pathologists are in up-to-date practices throughout the world. They, and all medical practitioners, are just beginning to delve into the nanotechnical wave. Nanotechnology refers to the structure and activity of minute particles, molecules, compounds, and atoms. By 2050, as nanotechnical studies develop further, new diseases and variations of old diseases will be discovered. Aggregation of medical data from billions of people, a process known as crowd sourcing, will be digitally interconnected to the new findings with computers. Pediatric pathologists will contribute to this expanding science with new laboratory instruments, including ultramodern microscopes known as Omniscopes. Robots will be programmed to perform autopsies and process surgical specimens. Analyzers in chemistry, microbiology, hematology, and genetics will, in 2050, produce dozens or even hundreds of results within minutes. These advances will lead to better treatments and overall better health for everyone.

BioJotter: A Biological Notepad

Article

Full-text available

Jan 2011

The watershed moment of genomics, a High-throughput sequencing technology promises to change the current scenario of computational genomics and comparative biology by delivering the tens of thousands of genome in the near future. To deal with huge genomic sequences, biologically compatible notepad is highly required therefore, in order to make biological sequence handling easy, an intuitive biotext editor for biological sequences has been developed, named as BioJotter. We have incorporated additional functions to this tool to interpret and visualize the the biological sequence puzzles, and make it easy-to-use and easy to understand interface. This small biological notebook is capable to do the analysis on the run and display the result in user friendly manner. BioJotter is efficient to handle large dataset, and useful for all users ranging from non-biologists to an expert bioinformaticians. This Notepad can be a replacement for commonly used Microsoft Notepad. BioJotter code is written in Perl 5.10 and Perl/Tk modules.

Structural and Evolutionary Considerations for Multiple Sequence Alignment of Rna, and the Challenges for Algorithms That Ignore Them

Chapter

Full-text available

Jan 2004

This chapter discusses the biological motivations for aligning data and explores the limitations of strict algorithmic approaches, focusing on the alignment of structural RNAs, or ribosomal RNA (rRNA) and transfer RNA (tRNA) sequences, for phylogenetic analysis. It emphasizes the importance of including both structural and evolutionary information in post-algorithmic manual curation of alignments. The chapter also suggests that further development of RNA alignment benchmarks, better substitution scoring matrices, and adaptation of techniques used in state-of-the-art protein alignments will lead to better algorithms for aligning RNA.

Protein Structural Statistics with PSS

Article

Aug 2013
J CHEM INF MODEL

Characterizing the variability within an ensemble of protein structures is a common requirement in structural biology and bioinformatics. With the increasing number of protein structures becoming available, there is a need for new tools capable of automating the structural comparison of large ensemble of structures. We present Protein Structural Statistics (PSS), a command-line program written in Perl for Unix-like environments, dedicated to the calculation of structural statistics for a set of proteins. PSS can perform multiple sequence alignments, structure superpositions, calculate Cartesian and dihedral coordinate statistics, and execute cluster analyses. An HTML report that contains a convenient summary of results with figures, tables, and hyperlinks can also be produced. PSS is a new tool providing an automated way to compare multiple structures. It integrates various types of structural analyses through an user-friendly and flexible interface, facilitating the access to powerful but more specialized programs. PSS is easy to modify and extend, and is distributed under a free and open source license. The relevance of PSS is illustrated by examples of application to pertinent biological problems.

The Quickhull Algorithm for Convex Hulls

Article

Full-text available

Jan 1993

The convex hull of a set of points is the smallest convex set that contains the points. This article presents a practical convex hull algorithm that combines the two-dimensional Quickhull Algorithm with the general-dimension Beneath-Beyond Algorithm. It is similar to the randomized, incremental algorithms for convex hull and Delaunay triangulation. We provide empirical evidence that the algorithm runs faster when the input contains nonextreme points and that it uses less memory. Computational geometry algorithms have traditionally assumed that input sets are well behaved. When an algorithm is implemented with floating-point arithmetic, this assumption can lead to serious errors. We briefly describe a solution to this problem when computing the convex hull in two, three, or four dimensions. The output is a set of "thick" facets that contain all possible exact convex hulls of the input. A variation is effective in five or more dimensions.

Comparative Protein Modelling by Satisfaction of Spatial Restraints

Article

Full-text available

Jan 1994

ModView, visualization of multiple protein sequences and structures

Article

Full-text available

Feb 2003

We describe ModView, a web application for visualization of multiple protein sequences and structures. ModView integrates a multiple structure viewer, a multiple sequence alignment editor, and a database querying engine. It is possible to interactively manipulate hundreds of proteins, to visualize conservative and variable residues, active and binding sites, fragments, and domains in protein families, as well as to display large macromolecular complexes such as ribosomes or viruses. As a Netscape plug-in, ModView can be included in HTML pages along with text and figures, which makes it useful for teaching and presentations. ModView is also suitable as a graphical interface to various databases because it can be controlled through JavaScript commands and called from CGI scripts. Availability: ModView is available at http://guitar.rockefeller.edu/modview.

Protein family annotation in a multple alignment viewer

Article

Full-text available

Apr 2003

The Pfaat protein family alignment annotation tool is a Java-based multiple sequence alignment editor and viewer designed for protein family analysis. The application merges display features such as dendrograms, secondary and tertiary protein structure with SRS retrieval, subgroup comparison, and extensive user-annotation capabilities. Availability: The program and source code are freely available from the authors under the GNU General Public License at http://www.pfizerdtc.com Contact: jason_johnson@merck.comenoch_huang@cambridge.pfizer.com *To whom correspondence should be addressed †Present address: Rosetta Inpharmatics, 12040 115th Avenue NE, Kirkland, WA 98034, USA

SWISS-MODEL: an automated protein homology-modeling server

Article

Full-text available

Aug 2003
NUCLEIC ACIDS RES

SWISS-MODEL (http://swissmodel.expasy.org) is a server for automated comparative modeling of three-dimensional (3D) protein structures. It pioneered the field of automated modeling starting in 1993 and is the most widely-used free web-based automated modeling facility today. In 2002 the server computed 120 000 user requests for 3D protein models. SWISS-MODEL provides several levels of user interaction through its World Wide Web interface: in the ‘first approach mode’ only an amino acid sequence of a protein is submitted to build a 3D model. Template selection, alignment and model building are done completely automated by the server. In the ‘alignment mode’, the modeling process is based on a user-defined target-template alignment. Complex modeling tasks can be handled with the ‘project mode’ using DeepView (Swiss-PdbViewer), an integrated sequence-to-structure workbench. All models are sent back via email with a detailed modeling report. WhatCheck analyses and ANOLEA evaluations are provided optionally. The reliability of SWISS-MODEL is continuously evaluated in the EVA-CM project. The SWISS-MODEL server is under constant development to improve the successful implementation of expert knowledge into an easy-to-use server.

Sur la Sphere Vide

Article

Jan 1934

BN Delaunay

Protein family annotation in a multiple alignment viewer.

Article

Jan 2003

Sali, A. & Blundell, T. L. Comparative modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815

Article

Jan 1994

We describe a comparative protein modelling method designed to find the most probable structure for a sequence given its alignment with related structures. The three-dimensional (3D) model is obtained by optimally satisfying spatial restraints derived from the alignment and expressed as probability density functions (pdfs) for the features restrained. For example, the probabilities for main-chain conformations of a modelled residue may be restrained by its residue type, main-chain conformation of an equivalent residue in a related protein, and the local similarity between the two sequences. Several such pdfs are obtained from the correlations between structural features in 17 families of homologous proteins which have been aligned on the basis of their 3D structures. The pdfs restrain C alpha-C alpha distances, main-chain N-O distances, main-chain and side-chain dihedral angles. A smoothing procedure is used in the derivation of these relationships to minimize the problem of a sparse database. The 3D model of a protein is obtained by optimization of the molecular pdf such that the model violates the input restraints as little as possible. The molecular pdf is derived as a combination of pdfs restraining individual spatial features of the whole molecule. The optimization procedure is a variable target function method that applies the conjugate gradients algorithm to positions of all non-hydrogen atoms. The method is automated and is illustrated by the modelling of trypsin from two other serine proteinases.

Multiple sequence alignment with CLUSTAL X

Article

Nov 1998
TRENDS BIOCHEM SCI

Guidelines for submitting commentsPolicy: Comments that contribute to the discussion of the article will be posted within approximately three business days. We do not accept anonymous comments. Please include your email address; the address will not be displayed in the posted comment. Cell Press Editors will screen the comments to ensure that they are relevant and appropriate but comments will not be edited. The ultimate decision on publication of an online comment is at the Editors' discretion. Formatting: Please include a title for the comment and your affiliation. Note that symbols (e.g. Greek letters) may not transmit properly in this form due to potential software compatibility issues. Please spell out the words in place of the symbols (e.g. replace “α” with “alpha”). Comments should be no more than 8,000 characters (including spaces ) in length. References may be included when necessary but should be kept to a minimum. Be careful if copying and pasting from a Word document. Smart quotes can cause problems in the form. If you experience difficulties, please convert to a plain text file and then copy and paste into the form.

Cn3D: Sequence and structure views for Entrez

Article