bioinformatics tools for structural biologystructural biolog · 2009-07-24 · bioinformatics tools...

Bioinformatics Tools - Dr Jaime Prilusky - 2006

Bioinformatics Tools for Bioinformatics Tools for Structural BiologStructural Biology

Dr Jaime PriluskyISPC-WISVienna, June 2006


Choose targetChoose target

ExpressionExpression

AbandonAbandon

SolubleSoluble RefoldRefold

PurifyPurify

Evaluate purity and function


Structure Determination


AbandonAbandon

Clone geneClone geneModify geneModify geneOther expression

systemsOther expression

systems

AbandonAbandonCrystallizationCrystallization

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--NMR NMR

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besides many intelligent approaches …

… targeted mutagenesis of surface patches containing, residues with large flexible side chains and their replacement with, smaller amino acids lead to effective preparation of X-ray quality, crystals of proteins otherwise recalcitrant to crystallization …

Derewenda ZS, Rational protein crystallization by mutational surface engineering. Structure. 2004 Apr;12(4):529-35.


the overall gene2structure process still is …


Choose targetChoose target

ExpressionExpression

AbandonAbandon

SolubleSoluble RefoldRefold

PurifyPurify





AbandonAbandon

Clone geneClone geneModify geneModify geneOther expression

systemsOther expression

systems

AbandonAbandonCrystallizationCrystallization

-

+

+

-+

-

-

+

+

--NMR NMR

-


http://www.weizmann.ac.il/ISPC/biotools.html

• Target Identity and Foldability• Selection of Expression System• Selection of Crystallization Conditions• Data Awarness• Data Management


OCA

OCA© facilitates the understanding of the genomics/proteomics biological data through data analysis and synthesis. The data integration process brings together dispersed pieces of information, generating comprehensive summaries that might be just what a researcher needs for crystallizing an idea or understanding a problem.

http://bip.weizmann.ac.il/oca

Web Services Enabled


SeqFacts©

SeqFacts© is a tool for sequence identification, analysis, characterization and annotation. This server will try to find relevant information related to your sequence.

http://bip.weizmann.ac.il/sqfbin/seqfacts


sequence

properties

references

DB similarity

RecentReferences

SeqAlert(once)

FoldIndex

SeqFacts

RecentReferences

Amino AcidDNA

similarity searchspecific DB search

quality cleaningvectors removal

calculationcalculationORF


Automatic analysis of 1226_int11f-SP6-19 (Sun Jun 8 15:55:24 2003)-------------------------------------------------------------------------------Summary:This analysis is based on a clean portion (4 to 644) from the 920 original bases. The best ORF of the six frames translation has a length of 186.A similarity search found 50 hits on 18 organisms: Oryctolagus cuniculus and Homo sapiens are the most representatives. Conserved domains present in the translated sequence: Arylesterase, COG3386.

Original files:1226_int11f-SP6-19.fasta1226_int11f-SP6-19.gcgORFs Six Frames translationSimilarity SearchConserved Domain databaseGenome DrosophilaGenome HomoGenome MusGenome RattusFantom (Functional Annotation Of Mouse)Taxonomy


FoldIndex

FoldIndex© tries to answer to the question: Will this protein fold?

FoldIndex© predicts whether a given protein is intrinsically disordered.Prilusky J., Felder C.E., Zeev-Ben-Mordehai T., Rydberg E., Man O., Beckmann J.S., Silman I. and Sussman J.L. Bioinformatics, 2005 Aug 15;21(16):3435-8

http://bip.weizmann.ac.il/fold



T.Zeev-Ben-Mordehai, EH.Rydberg, A.Solomon, L.Toker, VJ.Auld, I. Silman, S. Botti and JL. Sussman: The Intracellular Domain of the Drosophila CholinesteraseLike Neural Adhesion Protein, Gliotactin, is Natively Unfolded. PROTEINS: Structure, Function, and Genetics

53:758–767 (2003)


Web Services’ access to FoldIndex:

http://bip.weizmann.ac.il/fldbin/findex?sq=SEQ&m=xml

sq is the protein sequence, one character, no spaces.

m (mode) is either xml or efam, the format FoldIndex will return the result on. With the mode set to ‘xml’, the server sends results in XML format. When mode is equal to ‘efam’, the results are sent in eFamily format.

FoldIndex home page has sample Perl scripts to retrieve and parse prediction data.



BestPrimers

BestPrimers© provides a simple interface for primers calculation, with FoldIndex© support.

http://bip.weizmann.ac.il/sqfbin/bestPrimers



MultiPrimers

MultiPrimers© provides a simple interface for multiple primers calculation, with domain, enzyme and universal primers support.


VerifyCloning©

VerifyCloning© compares your original sequence against the result from cloning procedures, highlighting conflicting areas. VerifyCloning has an automatic reverse/complement mode that will reorder your sequences if required.

http://bip.weizmann.ac.il/vfclon



SuggestES©

SuggestES© takes the protein sequence you provide and scans a large database with protein sequences with known results for different expression systems, generating a suggestion based on several parameters:

Similarity: how similar is your sequence to the existing data in the database? Recentness: how recently was a given expression system used? Frequency: how frequently was a given expression system used?

http://bip.weizmann.ac.il/suggestES



SuggestXC©

SuggestXC© takes the protein sequence you provide and scans a large database with protein sequences with known results for different crystallization conditions, generating a suggestion based on several parameters:

Similarity: how similar is your sequence to the existing data in the database? Recentness: how recently was a given crystallization condition used? Frequency: how frequently was a given crystallization condition used?

http://bip.weizmann.ac.il/suggestXC



SeqAlert

SeqAlert© is a sequence alerting service that will periodically compare your sequence(s) against sequences from determined 3D structures, or structures being determined at PDB, and TargetDB, the database of target sequences from worldwide structural genomics projects.

It also reports the Pubmed IDs of papers that might be related to your sequence, published on the last 20 days.

http://bip.weizmann.ac.il/seqalert


Proteomics LIMS

An integrated Laboratory Information Management Systems for Proteomics with Complexes support.


http://www.weizmann.ac.il/ISPC/


LabTargets (browser/database for proteomics)

supported operating systems

required software

client-server architecture

generates/exports

• SPINE xml• TargetDB xml• Targets Status Graph• Targets Detail• Structures Gallery


• OCA (browser/database for structure & function)• SeqFacts (tell me something about this sequence)• FoldIndex (will this protein fold?)• BestPrimers (just best primers)• MultiPrimers (domain’s aware)• VerifyCloning (check results from DNA sequencing)• SuggestES (suggest an expression system)• SuggestXC (suggest crystallization conditions)• RecentReferences (what people published?)• SeqAlert (someone else works on this sequence?)• LIMS (including support for complexes)• LabTargets (browser/database for proteomics)

Some of our tools:


Direct Web Access

Web Services, Bulk Access

Web Services, Software Integration

How can you access our tools?


OCA mirrors world distribution

Direct Web Access

http://bip.weizmann.ac.il/oca


Web Services, Bulk Access

Beer Sheva, Israel Cambridge, USAChicago, USAHawaii, USAHelsinki, Finland

Leipzig, GermanyMissouri, USAMontpellier, FranceSan Diego, USA

Bangalore, IndiaKansas City, USAMadrid, Spain

FoldIndex

LPC CSU

OCA


Web Services, Software IntegrationIBS: Integrated Bioinformatics System@ KISTI, Daejeon, South Korea[FoldIndex, BestPrimers, SeqFacts, SuggestES]

GUTSS: Genome Structure Selection System@ The Burham Institute, La Jolla CA, USA[SeqFacts]

Raptor 3D: functional annotations to structures@ GBF, Braunschweig, Germany[OCA]

WIS LIMS:@ Weizmann Institute, Rehovot, Israel[OCA, FoldIndex, SeqFacts, BestPrimers, …]


Some of our tools allow for alocal installation

Why to have a local installation?

• intranet requirements• repetitive batch analysis• tight services integration


Software and languages used …

• Apache, the Apache Software Foundation.• Bundle::DataMint, © 2003, Jaime Prilusky, WIS, modules for Data

Mining and Data Integration.• mysql, © 1995-2003 MySQL AB.• flip, © 1997 OGMP (Organelle Genome Megasequencing Project)• OCA, © 2000-2005, Jaime Prilusky, WIS• Perl, © 1987-2001, Larry Wall.• phred, © 1993-2002 by Phil Green and Brent Ewing.• primer3, © 1996,1997,1998 Whitehead Institute for Biomedical

Research.• JMOL, Java molecular viewer for three-dimensional chemical

structures.


Dr. Shira AlbeckAnna BranzburgRani BravdoProf. Yigal BursteinDr. Orly DymYossi JacobovitchNurit LevyRan Meged

Yigal MichaelDr. Yoav Peleg Dr. Jaime PriluskyProf. Gideon SchreiberProf. Israel SilmanProf. Joel L SussmanDr. Tamar Unger

Israel Structural Proteomics Center


Dr Jaime Prilusky

[email protected]

bioinformatics tools for structural biologystructural biolog · 2009-07-24 · bioinformatics tools...

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