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The use of bioinformatics in drug discovery
 

Ten important bioinformatics databases

NameURLDescription
GenBank/DDBJ/EMBLwww.ncbi.nlm.nih.govNucleotide sequences
Ensemblwww.ensembl.orgHuman/mouse genome
PubMedwww.ncbi.nlm.nih.govLiterature references
NRwww.ncbi.nlm.nih.govProtein sequences
SWISS-PROTwww.expasy.chProtein sequences
InterProwww.ebi.ac.ukProtein domains
OMIMwww.ncbi.nlm.nih.govGenetic diseases
Enzymeswww.chem.qmul.ac.ukEnzymes
PDBwww.rcsb.org/pdb/Protein structures
KEGGwww.genome.ad.jpMetabolic pathways

 

Twelve important software programs in bioinformatics

CategoryNameURLDescription
Database SearchSRSsrs.ebi.ac.ukDatabase search 
 Entrezwww.ncbi.nlm.nih.govDatabase search 
 BLASTwww.ncbi.nlm.nih.govHomology search 
 DALIwww.ebi.ac.ukStructure database search 
Multiple alignmentClustalWwww.ebi.ac.ukMultiple sequence alignment 
 Tcoffeeigs-server.cnrs-mrs.fr/
Tcoffee/
Multiple Sequence Alignment 
PredictionGenScangenes.mit.eduGene prediction 
 PredictProteincubic.bioc.columbia.eduProtein structure prediction 
 Mfoldwww.bioinfo.rpi.eduRNA structure prediction 
PhylogeneticsPhylipbioweb.pasteur.fr/intro-uk.htmlTree reconstruction 
Editing/VisualizationJalviewwww.es.embnet.orgAlignment editor 
 Rasmolwww.bernstein-plus-sons.com/software/rasmol/Structure visualization 

 

Ten bioinformatics resource locators

NameURLDescription
ExPASywww.expasy.chDedicated to proteins
ArrayExpresswww.ebi.ac.uk/microarray/DNA chips
Swbicwww.swbic.orgMiscellaneous links
Pasteurbioweb.pasteur.fr/intro-uk.htmlMiscellaneous links; many online tools
RNA Worldwww.imb-jena.de/RNA.htmlRNA-related links
Phylipevolution.genetics.washington.edu/Everything on phylogeny
NCBI primerswww.ncbi.nlm.nih.gov/educationVery good primers on many subjects
Bielefeldbibiserv.techfak.uni-bielefeld.de/intro/dist.htmlAwesome online course
Bio-informerwww.ebi.ac.uk/Information/News/The EBI online news
Coffee Cornerwww.ncbi.nlm.nih.govOnline protein news

 

Essential Websites 

AddressDescription
www.ncbi.nlm.nih.gov/entrez/The top site for bibliographic information in biomedical sciences
www.expasy.org/sprot/The best starting point for finding out about proteins and their genes
www.ncbi.nlm.nih.govThe US site of the joint international DNA sequence repository (GenBank)
www.ebi.ac.uk/embl/Its counterpart in Europe (EMBL)
www.ddbj.nig.ac.jpIts counterpart in Japan (DDBJ)
www.ncbi.nlm.nih.gov/BLAST/The main site to compare your sequence with all others
pir.georgetown.eduA user-friendly site for analyzing your protein sequence and trying your first multiple sequence alignment with CLUSTALW

 

DNA chips and micro-arrays

AddressDescription
cmgm.stanford.edu/pbrown/A leading laboratory offering a complete "do-it-yourself" tutorial on micro-arrays
research.nhgri.nih.gov/microarray/main.htmlA great resource from the U.S. National Institutes of Health
www.ebi.ac.ukThe public repository for micro-array data from the European Bioinformatics Institute
www.affymetrix.comThe leading company in DNA chips
www.axon.comNice pictures and animations from a leading provider of micro-array readers

 

Genomic information

AddressDescription
www.ncbi.nlm.nih.govThe US site of the joint international DNA sequence repository (GenBank)
www.tigr.org/tdb/The Institute of Genomic Research: microbial genomics
www.ensembl.orgThe place to find out about the human genome
genome.cse.ucsc.eduAnother user-friendly human genome browser

 

Protein sequences

AddressDescription
www.expasy.org/sprot/The Expasy/SWISS-PROT server
pir.georgetown.eduThe Protein Information Resource server

 

Biochemistry

AddressDescription
www.glycosuite.comThe glycan structure database
lipid.bio.m.u-tokyo.ac.jpThe ultimate lipid database
chem.sis.nlm.nih.gov/chemidplus/ChemIDplus: Identifying molecules by drawing them up!

 

Biochemical pathways and enzymes

AddressDescription
www.expasy.ch/cgi-bin/search-biochem-indexFind which metabolic pathway a molecule belongs to.
www.genome.ad.jp/kegg/The famous Kyoto Encyclopedia of Genes and Genomes (KEGG). E.C. (Enzyme Codes) numbers or gene names are the best starting points for this resource.
brenda.bc.uni-koeln.de

The comprehensive enzyme information system BRENDA.

www.chem.qmul.ac.uk/iubmbThe official site for enzyme nomenclature of the International Union of Biochemistry and Molecular Biology (IUBMB).
www.ecocyc.orgThe Encyclopedia of E. coli Genes and Metabolism. It is progressively extending to other bacteria.

 

3-D structure information resources

AddressDescription
www.rcsb.org/pdbPDB, the official repository database for protein 3-D structures.
www.ncbi.nlm.nih.gov/StructureMMDB, NCBI's database of macromolecular 3-D structures with visualization tools.
scop.mrc-lmb.cam.ac.uk/scop

SCOP, a Structural Classification Of Proteins.

www.biochem.ucl.ac.uk/bsm/cath_newCATH (Class, Architecture, Topology, Homologous superfamily), a hierarchical classification of protein structures.
www.expasy.ch/swissmod/SWISS-MODEL.htmlSwiss-Model, a fully automated protein structure homology-modeling server.

 

Specialized protein databases

AddressDescription
imgt.cines.frIMGT, the International Immunogenetics database, specializes in proteins involved in the immune response.
rebase.neb.comRebase, the reference restriction-modification enzyme database.
afmb.cnrs-mrs.fr/CAZY

CAZy, an information resource on enzymes that degrade, modify, or create glycosidic bonds.

www.merops.co.ukMEROPS, a database specializing on proteases.
pkr.sdsc.edu/html/index.shtmlPKR, the Protein Kinase Resource, focuses on the protein kinase family of enzymes.
nrr.georgetown.eduNRR, the Nuclear Receptor Resource, is a collection of individual databases on the steroid and thyroid hormone receptors.
senselab.med.yale.edu/senselabThe Human Brain Database provides information on the proteins involved in neural processes, such as ion channels, membrane receptors of neurotransmitters and neuromodulators, as well as olfactory receptors (ORDB).
www.ncbi.nlm.nih.gov/COGThe COG (Cluster of Orthologous Groups) database regroups proteins shared by at least three major phylogenetic lineages (ancient conserved domains).

 

DNA analysis

AddressDescription
VecScreen_docsScreen your sequence for vector contamination
repeatmasker.genome.washington.eduTools for detecting and masking repeats
www.firstmarket.com/cutter/cut2.html
biotools.umassmed.edu/bioapps/rsites.html
rebase.neb.com
Sites to compute restriction maps for your sequence
biotools.umassmed.eduDesigning PCR primers
bioweb.pasteur.frTools for various DNA composition analyses
arbl.cvmbs.colostate.edu/molkit/
www.ch.embnet.org
Two sites for interactive dot-plot analysis
www.ncbi.nlm.nih.gov/gorf/gorf.htmlA basic ORF finder
opal.biology.gatech.edu/GeneMark
www2.ebi.ac.uk/genemark/
Gene prediction in prokaryotes using GeneMark
argon.cshl.org/genefinder/
corba.ebi.ac.uk/cgi-bin/sp/wrapper.cgi
genome.cs.mtu.edu/aat/aat.html
Various sites for predicting protein-coding genes in eukaryote DNA sequences
genes.mit.edu/genomescanFor predicting complete gene structures from vertebrate DNA sequences
bio.ifom-firc.it/ASSEMBLY/assemble.htmlA straightforward Web-service for small-scale gene assembly
www.mrc-lmb.cam.ac.uk/pubseq/
staden_home.html

www.phrap.org
www.tigr.org/software
www.acedb.org
Popular software for assembling and managing DNA sequences (you need to install them on your computer)
www.genecodes.com
www.dnastar.com
www.paracel.com
Main commercial sequence assembly software

 

Searching motifs in DNA sequences

AddressDescription
transfac.gbf.de/TRANSFAC/Search for potential transcriptional elements using the TRANSFAC database
bimas.dcrt.nih.gov/molbio/matrixs/Search for transcriptional elements using the IMD database
bimas.dcrt.nih.gov/molbio/proscan/Predict putative eukaryotic promoter regions
www.gsf.de/biodv/genomeinspector.htmlDetect distance correlations between sequence elements
www.dna.affrc.go.jp/htdocs/PLACE/
signalscan.html
Detect regulatory signals in plant sequences
meme.sdsc.edu/meme/website/Discover motifs in groups of related DNA or protein sequences
rsat.ulb.ac.be/rsat/Tools to analyze regulatory sequences

 

Main protein motif and domain collections sites

AddressDescription
www.expasy.ch/prositeThe PROSITE sequence signature database - curated
www.sanger.ac.uk/Software/PfamThe PfamA domain signature database - curated
www.sanger.ac.uk/Software/PfamThe PfamB domain signature database - automatically generated
www.tigr.org/TIGRFAMsThe TIGRFAM domain signature database -curated
www.bioinf.man.ac.uk/dbbrowser/PRINTSThe PRINTS domain signature database -curated
smart.embl-heidelberg.deThe SMART domain signature database -curated
blocks.fhcrc.orgThe BLOCKS alignment database - automatically generated
www.ebi.ac.uk/interpro/scan.htmlThe InterPro domain signature database
www.ncbi.nlm.nih.gov/Structure/
cdd/wrpsb.cgi
NCBI's conserved protein domain detector
prodes.toulouse.inra.fr/prodom/2002.1/htmlThe PRODOM alignment database - automatically generated

 

Protein sequence analysis over the Internet

AddressDescription
www.expasy.ch/toolsThe Expasy server
pir.georgetown.eduThe Protein Information Resource server
www.cbs.dtu.dk/servicesProtein analysis in Denmark
npsa-pbil.ibcp.frProtein analysis in Lyon, France
hits.isb-sib.ch/Protein domain analysis in Switzerland

 

ExPASy servers around the world

CountryURL
USAus.expasy.org
Canadaca.expasy.org
Chinacn.expasy.org
Taiwantw.expasy.org
Koreakr.expasy.org
Australiaau.expasy.org

 

BLAST and PSI-BLAST servers around the world

Country or ContinentProgram
USABLAST/PSI-BLAST
EuropeBLAST
EuropeBLAST
JapanBLAST/PSI-BLAST

 

Alternative methods for homology searches

Country or ContinentProgram
USAFASTA
USABLAT
EuropeFASTA
EuropeSSEARCH
JapanSSEARCH/FASTA

 

Various flavors of dot-plot programs

NameUsed ForRangePlatforms
DotletProteins, DNA10,000All
DnadotProteins, DNA100,000All
DotterProteins, DNA100,000Unix, Linux, Windows
DottupComplete genomes, DNA>100,000Unix, Linux

 

Online pairwise alignment programs

NameAlignment Type
lalignGlobal/Local
lalignGlobal/Local
alionGlobal/Local
alignGlobal/Local
alignGlobal/Local
xenAliTwoLocal for DNA
Blast2seqsLocal BLAST
Blast2seqsLocal BLAST

 

Online pairwise alignment analyses

NameURLFunction
lalnviewwww.expasy.ch/tools/sim-prot.htmlVisualization
prsswww.ch.embnet.org/software/PRSS_form.htmlEvaluation
prssfasta.bioch.virginia.edu/fasta/prss.htmEvaluation
graph-aligndarwin.nmsu.edu/cgi-bin/graph_align.cgiEvaluation

 

BLAST servers integrating multiple alignment methods

URLWhat You Can Do There
www.expasy.ch/cgi-bin/BLASTEMBnet-CH.plExtract entire sequences;
Export sequences in FASTA;
Submit sequences to ClustalW;
Submit sequences to Tcoffee
npsa-pbil.ibcp.fr/cgi-bin/npsa_automat.pl?page=npsa_blast.htmlExtract entire sequences;
Extract sequence fragments;
Export sequences in FASTA;
Submit sequences to ClustalW
srs.ebi.ac.ukSubmit sequences to ClustalW

 

ClustalW servers

NameLocationURL
EBIEuropewww.ebi.ac.uk/clustalw/index.html
EMBnetEuropewww.ch.embnet.org/software/ClustalW.html
PIRUSApir.georgetown.edu/pirwww/search/multaln.html
BCMUSAsearchlauncher.bcm.tmc.edu/multi-align/multi-align.html
GenomeNetJapanclustalw.genome.ad.jp
DDBJJapanwww.ddbj.nig.ac.jp/E-mail/clustalw-e.html
StrasbourgEuropeftp://ftp-igbmc.u-strasbg.fr/pub/ClustalW/

 

Other multiple sequence alignment resources over the Internet

MethodURL
Tcoffeeigs-server.cnrs-mrs.fr/Tcoffee/
www.ch.embnet.org/software/TCoffee.html
www.cmbi.kun.nl/bioinf/tools/T_COFFEE/
Dialignbibiserv.techfak.uni-bielefeld.de/
bioweb.pasteur.fr/seqanal/interfaces/dialign2-simple.html
DCAbibiserv.techfak.uni-bielefeld.de/cgi-bin/dca_submit

 

Motif-finding methods available online

MethodURL
Gibbs Samplerbioweb.pasteur.fr/seqanal/interfaces/gibbs-simple.html
bayesweb.wadsworth.org/gibbs/gibbs.html
Prattwww.ebi.ac.uk/pratt/index.html
eMotifdna.stanford.edu/emotif/
MEMEmeme.sdsc.edu/meme/website/
TEIRESIAScbcsrv.watson.ibm.com/Tspd.html
Bioprospectorbioprospector.stanford.edu
Improbizerwww.soe.ucsc.edu/~kent/improbizer/improbizer.html
BLOCK-Makerblocks.fhcrc.org/blocks/blockmkr/make_blocks.html

 

Sequence text conversion on the Web

NameURLDescription
FMTSEQtofu.tamu.edu/Pise/5.a/fmtseq.html
bioweb.pasteur.fr/seqanal/interfaces/fmtseq-simple.html
www.bimcore.emory.edu/Pise/
Converts almost every format, including ALN (the ClustalW format); sometimes modifies sequence names
READSEQanalysis.molbiol.ox.ac.uk/pise_html/readseq.html
dot.imgen.bcm.tmc.edu/seq-util/readseq.html
bio.indiana.edu/bioweb/seqanal/interfaces/readseq.html
bimas.dcrt.nih.gov/molbio/readseq/
www.ebi.ac.uk/readseq/index.html
A very popular tool for reformatting; does not recognize ALN
SEQCHECKwww.swbic.org/products/bioinfo/seqcheck/seqcheck.phpCleans your FASTA sequences

 

Multiple sequence alignment editing packages

NameURLDescription
Jalviewwww.ebi.ac.uk/clustalw/index.html
www.es.embnet.org/Doc/jalview/help.html
www.ebi.ac.uk/~michele/jalview/download.html
On the EBI server, Jalview access is offered after running ClustalW. A very complete package in Java, available online.
CINEMAwww.bioinf.man.ac.uk/dbbrowser/CINEMA2.1/Another complete package in Java. Needs to be installed locally; runs on most platforms.
Seaviewpbil.univ-lyon1.fr/software/seaview.htmlA very complete X-Window editor; very easy to install on a PC and very easy to interface with multiple sequence alignment programs.
Belvuwww.cgr.ki.se/cgr/groups/sonnhammer/Belvu.htmlVery convenient for removing redundancy; supports the Selex format.
Bioeditwww.mbio.ncsu.edu/BioEdit/bioedit.htmlUseful for editing RNA sequences; interfaces with BLAST.
DCSErrna.uia.ac.be/dcse/Can indicate secondary structures when editing RNA.
Reviewbioweb.pasteur.fr/cgi-bin/seqanal/review-edital.plA very complete (maybe exhaustive!) comparison of multiple sequence alignment editors.

 

Extracting information from a multiple sequence alignment

NameURLDescription
Logowww-lmmb.ncifcrf.gov/~toms/sequencelogo.html
www.cbs.dtu.dk/~gorodkin/appl/plogo.html
Logos
Blocksblocks.fhcrc.org/blocks/process_blocks.htmlIdentifies blocks in your multiple alignment
Blockgapwww.bork.embl-heidelberg.de/Alignment/blockgap.htmlMeasures blocks in your multiple alignment
Lamablocks.fhcrc.org/blocks-bin/LAMA_search.shLets you compare your multiple alignment with the BLOCKS database
Amaswww.compbio.dundee.ac.uk/servers/amas_server.htmlHelps you identify features in your multiple alignment

 

Multiple alignment beautifying tools

NameURLDescription
ESPriptprodes.toulouse.inra.fr/ESPript/cgi-bin/nph-ESPript_exe.cgiShading and coloring
Boxshadewww.ch.embnet.org/software/BOX_form.htmlShading in black and white
Mviewbioweb.pasteur.fr/seqanal/interfaces/mview_blast-simple.htmlCan process BLAST alignments

 

Predicting secondary structures

URLDescription
bioinf.cs.ucl.ac.uk/psipred/PsiPred for predicting protein secondary structures
cubic.bioc.columbia.edu/predictprotein
www.embl-heidelberg.de/predictprotein
www.cmbi.kun.nl/bioinf/predictprotein
www.sdsc.edu/predictprotein
PredictProtein for predicting protein secondary structures
www.rcsb.org/pdb/The Protein Database, containing every publicly available protein structure
www.ncbi.nlm.nih.gov/StructureThe NCBI section dedicated to structure analysis
www.rasmol.org
www.expasy.ch/swissmod/SWISS-MODEL.html
Two very popular PDB viewers (you must install them on your machine)
www.biochem.ucl.ac.uk/bsm/cath_new/
www2.ebi.ac.uk/dali/
scop.mrc-lmb.cam.ac.uk/scop
Popular structure classification collections
guitar.rockefeller.edu/modeller/modeller.html
www.expasy.ch/swissmod/SWISS-MODEL.html
Homology modeling
www.ncbi.nlm.nih.gov/Structure/RESEARCH/threading.html
compbio.ornl.gov/structure/prospect
Threading sequences onto PDB structures
folding.stanford.eduab-initio folding
www.scripps.edu/brooks
molmovdb.mbb.yale.edu/
MolMovDB Molecular dynamics
www.bio.vu.nl/nvtb/Docking.htmlProtein Interaction

 

Some RNA analysis resources

URLDescription
www.bioinfo.rpi.edu/applications/mfold/
bibiserv.techfak.uni-bielefeld.de/cgi-bin/mfold_submit
bioweb.pasteur.fr/seqanal/interfaces/mfold-simple.html
mfold.burnet.edu.au
The famous Zuker Mfold and some of its mirrors.
www.genetics.wustl.edu/eddy/tRNAscan-SEFinding tRNAs in a genome
www-unix.mcs.anl.gov/compbio/PatScan/HTML/matching_nucleotides.htmlFinding an RNA-like structure in a genome
www.esil.univ-mrs.fr/~dgaut/download/Finding an RNA structure in a genome (needs to be downloaded)

 

Ribosomal RNA resources on the Internet

URLDescription
rdp.cme.msu.eduProvides data and services, including online phylogenetic analysis.
rrna.uia.ac.be/lsuA European database on the larger of the two ribosomal subunits. It contains predicted structures. You can query the database online. This site features lots of online software.
rrna.uia.ac.be/ssuDedicated to the small ribosomal subunit.

 

Some non-coding RNA resources

URLDescription
mbcr.bcm.tmc.edu/smallRNA/smallrna.htmlDedicated to small non-coding RNAs.
rna.wustl.edu/tRNAdb/Dedicated to tRNAs.
bighost.area.ba.cnr.it/BIG/UTRHome/Dedicated to the untranslated regions of genes.
www.indiana.edu/~tmrna/Dedicated to the recently discovered tmRNA that are both transfer and messenger RNAs. (If you don't yet know what this is, you MUST take a look at this fascinating Web site!)

 

Generic RNA resources

URLDescription
www.imb-jena.de/RNA.htmlRNA World, one of the most complete sites currently available
www.rnabase.org/links/Another very complete site

 

Phylogenetic trees

URLDescription
www.ebi.ac.uk/clustalw/Use ClustalW to build multiple alignments and compute NJ trees.
www.genebee.msu.ru/clustal/basic.htmlThe Genebee server can produce genuine phylogenetic trees in one step.
www.es.embnet.org/Doc/jalview/ help.htmlYou can use Jalview to produce NJ trees. A very powerful tool that can combine alignment edition with tree computation.
sdmc.krdl.org.sg:8080/~lxzhang/phylip/A Web interface for Phylip. Many other phylogeny-related programs are also available online at the Pasteur site.
bioweb.pasteur.fr/seqanal/phylogeny/phylip-uk.htmlA Web interface for Phylip.
www.genebee.msu.ru/services/phtree_reduced.htmlVery powerful interface for a new tree reconstruction method.

 

Generic phylogenetic resources on the Internet

URLDescription
evolution.genetics.washington.edu/phylip/software.htmlJoe Felsenstein's pages, where Phylip lives; it's also one of the most extensive collections of resources available. Truly a legendary site!
www.ucmp.berkeley.edu/subway/phylo/phylosoft.htmlA very complete list of phylogeny resources.
paup.csit.fsu.edu/index.htmlThe home of PAUP, the other legendary phylogeny package. Although PAUP is a commercial package, it's reasonably priced and worth every penny, according to specialists.
www.ncbi.nlm.nih.gov/About/primer/phylo.htmlThe NCBI primer on phylogeny.
www.techfak.uni-bielefeld.de/bcd/Curric/MathAn/mathan.htmlA high-quality course on tree reconstruction methods.

 

Collections of orthologous sequences

URLDescription
www.ncbi.nlm.nih.gov/COG/Clusters of orthologous sequences maintained by the NCBI. Each cluster contains proteins from bacterial genomes.
pbil.univ-lyon1.fr/databases/hovergen.htmlA collection of orthologous vertebrate genes.
pbil.univ-lyon1.fr/databases/hobacgen.htmlA collection of orthologous bacterial genes.
systers.molgen.mpg.deAnother collection of homologous sequences.
rdp.cme.msu.edu/html/
rrna.uia.ac.be
Two extensive collections of ribosomal RNA sequences, which are very useful for classifying new organisms, and come with appropriate phylogenetic tools.

 

Ref: Bioinformatics For Dummies