Protein Structure and Function. Application of Bioinformatics Methods - John Rigden 2014

Comparative Protein Structure Modeling
Steps in Comparative Protein Structure Modeling

In comparative protein modeling, or template-based (Homology) modeling, the 3D Structure of a protein with an unknown structure (the target) is built based on the known structure of one or more related Proteins (templates) (Blundell et al. 1987; Fiser 2004; Ginalski 2006; Greer 1981; Marti-Renom et al. 2000; Petrey and Honig 2005). The prerequisites for obtaining a model of satisfactory quality are: a) a notable sequence similarity between the target and the template; and b) correct sequence alignment.

All modern comparative modeling Methods comprise five sequential steps. The first step involves searching for proteins with known 3D structures that are closely related to the target sequence. The second step is the Selection of structures to be used as templates. The third step is sequence alignment against the target sequence. The fourth step entails building the target model based on the alignment of its sequence with the template structures. The final step is Model Evaluation using various criteria.

There are several computer programs and web servers that automate the comparative modeling process (Table 3.1). Web servers are useful and user-friendly (Battey et al. 2007; Fernandez-Fuentes et al. 2007a; Rai et al. 2006; Y. Zhang 2007); however, the best results to date are achieved when experts use various modeling tools in a non-automated manner (Kopp et al. 2007). Making complex decisions regarding the selection of the most structurally and biologically appropriate templates, optimally combining diverse template information, refining alignments in non-trivial cases, selecting segments for loop modeling, incorporating Cofactors and ligands into models, and defining spatial restraints all require an expert approach that is difficult to fully automate (Fiser and Sali 2003a), although increasing efforts are being made in this direction (Contreras-Moreira et al. 2003; Fernandez-Fuentes et al. 2007b).

Class="center">Table 3.1. Names and URLs of several online tools useful for solving various comparative modeling tasks

Fold Recognition via database searching

BLAST/PSI-BLAST

www.ncbi.nlm.nih.gov/BLAST/

FastA/ SSEARCH

www.ebi.ac.uk/fasta33

FFAS03

ffas.ljcrf.edu/ffas-cgi/cgi/ffas.pl

Fold recognition via threading

PHYRE/3D-PSSM

www.sbg.bio.ic.ac.uk/~3dpssm

FUGUE

www-cryst.bioc.cam.ac.uk/~fugue

LOOPP

cbsuapps.tc.comell.edu/

MUSTER

zhang.bioinformatics.ku.edu/MUSTER

SAM-T06

www.soe.ucsc.edu/research/compbio/SAM_T06/T06-

Prospect

query.html compbio.oml.gov/structure/prospect

PSIPRED

bioinf.cs.ucl.ac.uk/psipred/psiform.html

UCLA-DOE

www.doe-mbi.ucla.edu/Services/FOLD

123D

123d.ncifcrf.gov

Sequence alignment tools

Smith-Waterman

jaligner.sourceforge.net/

ClustalW

www.ebi.ac.uk/clustalw/

Muscle

www.drive5.com/lobster/

T-COFFEE

tcoffee.vital-it.ch

PROMALS

prodata.swmed.edu/promals/promals.php

PROBCONS

probcons.stanford.edu

Comparative modeling, loop, and side-chain modeling

MMM

www.fiserlab.org/servers/MMM

M4T

www.fiserlab.org/servers/M4T

MODELLER

www.salilab.org/modeller/modeller.html

MODWEB

modbase.compbio.uesf.edu/ModWeb20-html/modweb.html

I-TASSER

zhang.bioinformatics.ku.edu/I-TASSER/

HHPRED

toolkit.tuebingen.mpg.de/hhpred

3D-JIGSAW

www.bmm.icnet.uk/servers/3djigsaw/

CPH-MODELS

www.cbs.dtu.dyk/services/CPHmodels/

COMPOSER

www.cryst.bioc.cam.ac.uk

SWISS-MODEL

swissmodel.expasy.org/workspace

FAMS

www.pharm.kitasato-u.ac.jp/fams

WHATIF

www.cmbi.kun.nl/whatif/

PUDGE

wiki.c2b2.columbia.edu/honiglab_public/index.php/Software

3D-JURY

meta.bioinfo.pl

RAPPER

mordred.bioc.cam.ac.uk/~rapper

ESYPRED3D

www.fundp.ac.be/sciences/biologie/urbm/bioinfo/esypred/

CONSENSUS

structure.bu.edu/cgi-bin/consensus/consensus.cgi

PCONS

pcons.net

Loop modeling

ARCHРRED

fiserlab.org/servers/archpred

MODLOOP

salilab.org/modloop

WLOOP

bioserv.rpbs.jussieu.fr/cgi-bin/

Side-chain modeling

SCWRL

dunbrack.fccc.edu/SCWRL3 .php

IRECS

irecs.bioinf.mpi-inf.mpg.de/index.php

Model evaluation

PROCHECK

www.biochem.ucl.ac.uk/~roman/procheck/procheck.html

Prosa-web

prosa.services.came.sbg.ac.at/prosa.php

WHATCHECK

swift.cmbi.ru.nl/gv/whatcheck

VERIFY3D

nihserver.mbi.ucla.edu/Verify_3D

ANOLEA

protein.bio.puc.cl/cardex/servers/anolea/

AQUA

urchin.bmrb.wisc.edu/~jurgen/Aqua/server/

PROQ

www.sbc.su.se/~bjom w/ProQ/ProQ.cgi


Last update: 06/08/2026

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