October 10, 2003

1
Demo Protein Information Resource

• October 10, 2003
• NIH Proteomics Workshop
• Bethesda, MD
• Raja Mazumder, Ph.D.
• Scientific Coordinator and Senior Protein
  Scientist, PIR

2
Database Demo

• NREF Database
• http//pir.georgetown.edu/pirwww/search/pirnref.sh
  tml
• NREF Entry (NF00091113)
• iProClass Database
• http//pir.georgetown.edu/iproclass/
• iProClass Sequence (A58910), Motif (PCM00487)
• PIR-PSD Database
• http//pir.georgetown.edu/pirwww/search/textpsd.sh
  tml
• PIR Entry (A58910)
• Other Molecular Databases
• Function KEGG Enzyme (EC 1.1.1.205), KEGG
  Pathway (MAP00230) BRENDA (EC 1.1.1.205)
• Structure PDB (1AK5), SCOP (Alanine Racemase),
  CATH (1AK5)
• Domain Pfam (PF00478), CDD (HemL)
• Classification COGs (COG0001)

3
PIR Web Site (http//pir.georgetown.edu)
4
Text Search Result
5
Text Search Result with NULL/NOT NULL
6
Peptide Search Results
7
PIR-NREF Search Result (I)
Test Sequence ftp//nbrfa.georgetown.edu/pir/mis
c/test.seq
8
PIR-NREF Search Result (II)
9
HMM Domain/Motif Search
10
PIR Pattern Search
11
PIR Pattern Search Result (I)

• http//pir.georgetown.edu/pirwww/search/patmatch.h
  tml

Pattern Match Sequence vs. PROSITE
12
PIR Pattern Search Result (II)

• Search a query pattern against a sequence
  database.

13
PIR Domain Display
14
PIR-NREF Database (http//pir.georgetown.edu/pirww
w/search/pirnref.shtml)
.

search
15
PIR-NREF Report
16
Related Sequences
17
PIR-iProClass Database
18
iProClass Sequence Report
19
PDB Structure of Molecule Inosine-5'-Monophospha
te Dehydrogenase
20
Development of protein sequence databases

• Atlas of protein sequence and structure Dayhoff
  (1966) first sequence database (pre-bioinformatics
  ). Currently known as Protein Information
  Resource (PIR)
• Protein data bank (PDB) structural database
  (1972) remains most widely used database of
  structures
• SWISSPROT protein sequence database (1987)
  still in use not exhaustive but heavily
  annotated
• UniProt The United Protein Databases (UniProt,
  2003) will create a central database of protein
  sequence and function by joining the forces of
  the SWISS-PROT, TrEMBL and PIR protein database
  activities

21
Protein Family Classification
Discovery of New Knowledge by Using Information
Embedded within Families of Homologous Sequences
and Their Structures

• Superfamily and Domain Classification
• Superfamily Concept
• End-to-End Similarity Same Overall Domain
  Architecture
• Significance
• Improve Sensitivity of Protein Identification
• Provide Complete Clustering for Database
  Organization
• Detect and Correct Genome Annotation Errors
  Systematically
• Drive Other Annotations
• Stimulate Evolution, Genomics and Proteomics
  Research

22
Protein Family/Superfamily Definitions

• Family
• A Set of Protein Sequences That Share a Common
  Evolutionary Ancestor with End-to-End Sequence
  Similarity (No Major Discrepancy by Standard
  Multiple Alignment Methods)
• Have the Same Domain Architecture (Except
  Incomplete or Alternately Spliced)
• Overall Sequence Identity ?
• Superfamily
• A Set of Protein Families That Share a Common
  Evolutionary Ancestor From End-to-end
• Have the Same Domain Architecture
• Overall Sequence Identity ?
• Best-hit rule

23
Protein Domain Definition

• Domain
• Domains can be described as discrete structurally
  conserved units in proteins that are evolutionary
  mobile
• They typically correspond to discrete globular
  folding units in the structure of a protein and
  may often occur independently of other domains in
  the protein
• A Recognizable Region of Similarity
• Have a Common Ancestry
• Found in Diverse Protein Sequences (in gt 2
  Superfamilies)
• A Sequence Can Belong to Only One Protein Family
  and Superfamily, but May Contain More Than One
  Domains.

24
Network structure of protein classification
P-loop NTPase (Structural fold) P-loop NTPase (Structural fold) P-loop NTPase (Structural fold)
Domain superfamilies Domain superfamilies Domain superfamilies
AAA ATPases DNA pumping ATPases RecA/SF1/SF2 helicase lineage
Homeomorphic families Homeomorphic families Homeomorphic families
Replicative DNA helicase ATPase Nucleic acid helicase
VACa-D5Rb MCV-MC094R SFV-gp080R FPV-FPV058 MSV-MSV089 AMV-AMV087 VAC-A32L MCV-MC140L SFV-gp120L FPV-FPV197 MSV-MSV171 AMV-AMV150 VAC-A18R MCV-MC123R SFV-gp108R FPV-FPV183 MSV-MSV148 AMV-AMV059
25
Network structure of protein classification
26
Superfamily-Domain-Motif Relationship
27
iProClass Superfamily List

• All Superfamilies Containing PF00001

28
iProClass Superfamily Report
29
Alignment and Tree View
30
PIR-Protein Sequence Database
31
PIR-PSD Entry
32
BLAST/FASTA Search
33
PIR FASTA Search Result
34
PIR Searches and Alignment
BLAST Search
35
PIR Hidden Markov Model

• http//pir.georgetown.edu/pirwww/search/pirhmm.htm
  l
• HMM Model Building Sequence Search
• One Protein Against All HMMs
• All Proteins Against One HMM

36
Bibliography Submission System
37
PIR Bibliography Submission

• View Bibliography Information
• View Protein Entry
• Submit Citation with Optional Categorization

38
PIR Bibliography Submission
39
Bibliography Information Display (I)

• From PIR-NREF
• From Other Curated Database

40
Bibliography Information Display (II)

• From User Submission
• From Computer-Mapping (e.g. Gene Symbol)

41
Proteomic Bioinformatics

• Large-Scale Analysis of Proteomic Data Homology
  Search for Pathways

42
PIR Batch retrieval
43
PIR Batch Retrieval Results
44
Pairwise Alignments
45
PIR Pairwise Alignment
46
Composition Molecular Weight Calculation
47
Composition Molecular Weight Calculation
48
PIR support center