Future%20CAMD%20Workloads%20and%20their%20Implications%20for%20Computer%20System%20Design

1
Future CAMD Workloads and their Implications
for Computer System Design

• IEEE 6th Annual Workshop on
  Workload Characterization

2
What is CAMD?

• Computer-Assisted Molecular Discovery used in
• drug discovery
• agrochemical discovery (herbicides, insecticides,
  etc.)
• cosmeceutical discovery
• common objectives of all CAMD applications
• find a small molecule (drug or ligand or
  active) with the right chemical structure
  for optimal
• interaction with large biomolecule (receptor or
  target or protein)
• ADMET properties (getting keeping ligand near
  receptor in body)
• decide which compounds (potential drugs) should
  be synthesized/purchased and tested (screened)
  next?
• decide by using computer to first do virtual
  screening

3
Molecular discovery process
Genomics, Proteomics
Target ID/Validation Structure
CAMD
Assay Development
Hits

• Bioinformatics

Lead Identification
Lead Optimization
Preclinical/ADMET
Clinical Trials

• Cheminformatics
• Modeling Simulation
• Decision Support

Sales Marketing
4
Three types of CAMD problems

• Intensive computations on one structure or
  complex
• getting 3D structure of target from genomic
  information
• protein folding problem a classic CAMD
  problem area
• parallel/distributable algorithms exist but
  best done on a single
  processor
• huge number of possible conformations ? short
  cuts taken
• refining 3D structure of target from X-ray/NMR
  data
• performing protein-ligand docking scoring
• virtual receptor-ligand complexation ? virtual
  screening
• flexibility of ligand is currently addressed
• flexibility of protein is rarely addressed due to
  ? cpu time
• scoring functions are crude due to ? cpu time
• faster cpus and more memory (for protein
  folding) would enable better quality results

5
Three types of CAMD problems

• Modest computations on MANY structures
• millions of real compounds billions of virtual
  cmpds
• many subtasks associated with virtual screening
  e.g.
• convert 2D structure of ligand to 3D
  (Concord)
• generate multiple conformations of each ligand 3D
  structure
• perform various ? cpu tests to identify which
  ligands merit further attention using ? cpu
  methods (e.g., docking)
• crude estimates of ADMET-related properties
  (e.g., solubility, membrane permeability, etc.)
• crude shape-complementarity tests
• perform docking (at increasing levels of
  accuracy)
• large input stream ? ideally suited for
  distributed proc.
• grid-computing using many thousands of nodes
  (and faster nodes) would enable better quality
  results

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Three types of CAMD problems

• Storing data for virtual compounds
• millions of real compounds billions of virtual
  cmpnds
• why store data for virtual compounds?
• costs time money to generate regenerate data
• science-related reasons
• data generated for one project is often useful
  for another
• must store data for each conformation of each
  structure
• must store data for each structure that a
  compound can adopt (Optive Research will
  introduce technology early next year)
• new technology will result in HUGE volumes of
  virtual data
• IP-related, competition-related reasons
• pharma industry is already planning for offensive
  and defensive needs in the coming
  virtual-screening and virtual-IP wars
• need means to store and access huge volumes of
  data

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Closing comments

• practitioners of CAMD are well aware that quality
  of current methods is limited by
  compute-resources
• rate of discovery and quality of actives
  discovered would both improve if CAMD methods
  improved
• given that the sales of many actives each exceed
  1 billion per year, the market for improved
  compute-power (and improved CAMD software)
  is quite substantial
• I sure hope that you computer architects can
  help!! -)

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Contact Info

• for questions about this short presentation,
  please feel free to contact me at
• Dr. Robert S. Pearlman, Pres. CSO
• Optive Research, Inc.
• 512-514-6222
• bob.pearlman_at_optive.com
• for questions about Optive Research, Inc. and/or
  about the Computer-Assisted Molecular Discovery
  software which we develop, contact me as
  indicated above or visit our web-site at
• www.optive.com