DTFNPACISDSC SAN Plans

1
The Integrative Biosciences Program Within
NPACI/SDSC As Exemplified by the PDB
2
PDB Background

• The PDB is vital biological infrastructure
  150,000 Web hits/day one file every second 7/24
  over ½ of all SDSCNPACI web access
• The NSF is the lead agency
• Protein structure is the focus
• as a follow on to the human
• genome project

3
PDB Relevance to Drug Discovery
Search Google for Protein The PDB comes up
number 1 gt Many novice users access the
PDB Our role is to educate this population,
examples 1. 2. On-line As developed by
Aston Taylor an NSF REU student in 2000.
4
What NPACI/SDSC Brings to PDB

• 7/24 (only off-line 3 hrs in 2000)
• Standards development and deployment (thrust)
• Large scale distributed databases (DAKS)
• Grid deployment (CE, electrostatics)
• Visualization (molecular biology toolkit)
• Outreach and Education

5
The Encyclopedia of Life
A National Proteomics Resource

• Integrates our existing strengths
• The largest biological computation ever
  undertaken

6
Almost everything in the body is either made
of proteins or made by them.
Matt Ridley, Genome The Autobiography of a
Species in 23 Chapters

• Types of Questions which can be addressed by
  EOL
• Is protein X found in anthrax?
• Is protein X a drug target, that is, does it
  exist predominantly in pathogenic bacteria or is
  it found in eukaryotes also?
• Has caspase-1, a protein involved in cell death
  and aging, been identified in any plants, if so
  what species and do the proposed protein
  structures look similar?
• Give me all available information on caspase-1

7
Computational Pipeline
800 genomes with 10k-20k ORFs (Open Reading
Frame) each107 ORFs/hours
Genome protein sequences
sequence info
structure info
Prediction of signal peptides (SignalP,
PSORT) transmembrane (TMHMM, PSORT) coiled
coils (COILS) low complexity regions (SEG)
NR, PFAM
SCOP, PDB
4 CPU years
104 entries
Building FOLDLIB PDB chains SCOP domains PDP
domains CE matches PDB vs. SCOP 90 sequence
non-identical minimum size 25 aa coverage (90,
gaps lt30, endslt30)

228 CPU years
Create PSI-BLAST profiles for Protein sequences
3 CPU years
Structural assignment of domains by PSI-BLAST on
FOLDLIB
Only sequences w/out A-prediction
9 CPU years
Structural assignment of domains by 123D on
FOLDLIB
Only sequences w/out A-prediction
252 CPU years
Functional assignment by PFAM, NR, PSIPred
assignments
3 CPU years
Domain location prediction by sequence
FOLDLIB
Store assigned regions in the DB
8
Initial PrototypeAnnotation of Arabidopsis
thaliana Proteins

• Prototype computation (one genome) took
• 40,000 hours on 4-64 processors at .1 TF
• Post-TeraGrid, computation (all genomes in EOL)
  will take
• 4,500 hours on 1000 processors at 5 TFs

Arabidopsis annotation joint work with SDSCand
Ceres