Jeremy Yang Software Systems Manager Division of Biocomputing Dept. of Biochemistry & Molecular Biology UNM School of Medicine

Cyberinfrastructure Day -- April 22, 2010

What is Biocomputing? Cyber Revolution (~1980-2010+) Cyberinfrastructure (To be or not to be?) Super Computing, Redefined

I. II. III. IV.

Division of Biocomputing http://biocomp.health.unm.edu/

Department of Biochemistry & Molecular Biology School of Medicine

Also affiliated with the NIH Roadmap-funded UNM Center for Molecular Discovery

  Biomolecular screening informatics

  Cheminformatics   Bioinformatics   Genomics   Virtual screening   Molecular modeling   SAR (Structure-

Activity-Relationship)

  Data mining, machine learning

  3D visualization   Public data integration   Collaborations in

chemistry, biology, medicine, comp sci

  BIOMED 505 course   Software development,

management, deployment & support

Larry Sklar, et al., UNMCMD (NIH Roadmap)

~$20M NIH awarded to date

 32 cpu Linux cluster  32GB RAM server  Linux: OpenSUSE, CentOS, RedHat, Fedora, Ubuntu  SGI/IRIX  Windows, Mac OS X  Automated integration with NIH databases

 2+ Oracle instances  PostgreSQL, MySQL  Stereo graphics workstation  25+ scientific software packages  Supported in-house applications

We are cyberinfrastructure users and providers!

Virtual chemistry; property prediction, chemspace navigation, computer aided molecular design, graph

theory, databases

 Nucleotide and protein sequence analysis  Genomics, proteomics  Merging with chemical biology, etc.

 Computational search for likely biological actives  Database may be real or virtual compounds  2D and 3D methods  2D similarity search  3D similarity search (shape, pharmacophore)  docking (3D, protein binding site)

Example: 3D shape search;

prozac & paxil

c/o OpenEye Rocs

atoms, bonds, surfaces, fields, interactions, stereo

serotonin

hemoglobin

Computational models for protein-ligand binding

interaction potential sites: hydrophobic (green), hydrophillic (purple), hbond acceptors (red)‏

Gleevec is a leukemia drug known to bind with Abl kinase.

Abl kinase (1iep.pdb)‏

Gleevec in binding site

http://video.google.com/videoplay?docid=-5859274887925224981#

http://chemapps.stolaf.edu/pe/protexpl/htm/top.htm?id=1d66&&&chpa=true

Jmol interactive DNA modeling demo:

PyMol movie:

Expert users can advance understanding via rich, dynamic, visual interfaces.

(Watch movies...)

E.g., Searching NIH PubChem for non-selectivity

Many biomedical data sources worldwide

SLIDE 15 (15 MIN?)

Division of Biocomputing in 2008

 Rapid change, challenge and opportunity  Learning from history, trends (new not enough)  Winners and losers  Science, experts have led and followed.  ~1980-2010 covers 3σ (99.7%)  And evolution...

 Rapid change, challenge and opportunity  Learning from history, trends  Winners and losers  Science, experts have led and followed.  ~1980-2010 covers 3σ (99.7%)  And evolution...

1977: Atari 2600 1978: Space Invaders 1981: IBM-PC (MS-DOS) 1983: cellphone 1983: GNU Project 1984: Neuromancer,

William Gibson, “cyberspace”

1984: Apple Mac, mouse, windows & icons

1985: Oracle 5 (client-server) 1989: Intel 486 Pentium (1M

transistors, 50MHz) 1990: MS Windows 3.0 1990: WWW (Berners-Lee) 1991: High Perf Comp &

Comm Act (Al Gore) 1991: Linux (Linux Torvalds) 1991: AOL 1991: ETrade

1993: Jurassic Park (via SGI) 1993: NCSA Mosaic 1994: Netscape Navigator 1994: “Good Times” hoax 1994: Match.com 1995: “Concept” virus (Word) 1995: Internet Explorer 1995: Apache project 1995: Yahoo!

1995: Amazon.com 1995: My mother gets email 1997: Google 1997: eBay 1999: Melissa virus (Outlook) 1999: Napster (p2p) 2000: MS convicted 2000: 3M USA broadband* 2000: dot-com bubble pops

*Fixed non dial-up internet connections >56k (FCC).

2000: 802.11b wireless 2001: Apple iPod 2001: Apple iTunes 2001: Wikipedia 2003: Skype 2005: YouTube 2005: Rio power grid hacked 2005: NSA domestic surveillance 2006: Facebook

2006: Amazon Cloud 2007: DOD hacked 2008: 70M USA broadband* 2009: Cyberdefense USA priority 2009: Twitter role in Iran election

protests 2010: UAVs are SOPs 2011: Cyber terrorism?

*Fixed non dial-up internet connections >56k (FCC).

The dotted line keeps moving...

Case study: database cheminformatics in pharma research, 1990→2000.

 In 1990, high speed chemical searching was beyond standard capabilities.  Research groups managed local servers in their labs & specialized DB engines (e.g. Daylight Inc.).  By 2000, this function had moved to IT (via Oracle cartridges, etc.) corporate informatics infrastructure  Transition not smooth, but very beneficial.

imidazoles

cocaine Standard functions:

substructure, similarity, identity

chemical searching

(1) office equipment (2) lab equipment (3) experimental apparatus (4) the experiment (5) a commodity (6) custom configured experimental

vehicle for exploration (5) all of the above

(1) office equipment (2) lab equipment (3) experimental apparatus (4) the experiment (5) a commodity (6) custom configured experimental

vehicle for exploration (5) all of the above

 Scientific software  Computational science  Commodity software  Engineering enables science  Science requires agile development, high performance, experimentation, risk taking, play.  Cyberinfrastructure users and developers/maintainers

SLIDE 30 (30 MIN?)

 Scientific research  Computational research  High performance computing as a research tool  High performance infrastructure as a productivity tool

 Scientific software for experts  Enabling software for scientists  Commoditization (e.g. cloud computing)  Plumbing vs. experimental apparatus  Appropriate tiers and domains

IT: “Poorly managed computers and needy ill-

trained users put the system at risk.”

Research: “We need power, flexibility and

access and not another lame PC.”

And with other cyberfolks too. And with great results.

 In ~5 yrs, super → un-super  Super computing? Define computer.  Advances from unexpected places:

  gaming, movies (graphics -- vs. AI)   social networking (crowdsourcing)   even business (web standards, UIs, security)

 Super computing is pushing the current limits  But where are the key frontiers?

Advances from unexpected places...

Colossus code breaking computer, UK.

Eniac computer, Univ of Pennsylvania.

Cray computer

SLIDE 40 (40 MIN?)

High performance (super) computing is pushing the current limits.

This is what a “computer” looks like.

“The network is the computer.” - John Gage (Sun, NetDay founder)

Corollaries:  The network is the (semantic) database  The network is cyberspace  The network is us too

 Super users → super computing  Blackbox AI/monolith paradigm limiting  Human/computer co-evolution

Cytoscape biological network

visualizer with drug - target interactions

“Super Computers” @ Division of Biocomputing  Tudor Oprea  Cristian Bologa  Stephen Mathias  Oleg Ursu  Jerome Abear  Ramona Curpan  Liliana Halip  Andrei Leitao

Jeremy Yang jjyang@salud.unm.edu

Cyberinfrastructure Day -- April 22, 2010

Happy Earth Day!