1. Nancy Baker SILS Bioinformatics Seminar January 21, 2004
Presentation of Recent Trends in Computer-aided Drug Discovery By Alexander Tropsha
Current Opinion in Drug Discovery & Development, 2000
Nancy Baker
SILS Bioinformatics Seminar
January 21, 2004

2. Terminology Overview
“ics” : genetics, genomics, proteomics, bioinformatics, chemoinformatics
Modifiers
Structural
Functional
Pharmaco
Informatics – general scientific discipline dealing with storage, analysis, and retrieval of information

3. Genetics Review DNA: TACGCTTCCGGATTCAA transcription RNA:
AUGCGAAGGCCUAAGUU
translation
Amino Acids:
PIRLMQTS
Protein

4. Overview Continued – A simple example
Protein
Small molecule drug

5. Overview Continued – A simple example
Protein
Small molecule drug
Protein
Protein disabled … disease cured

6. Bioinformatics Chemoinformatics Protein Large databases
Small molecule drug
Large databases
Large databases
Tropsha compares these. Let’s look at some of the comparisons he makes. Mutual similarity techniques.

7. Size of databases Millions of entries in databases
CAS : 23 million
GeneBank : 5 million
Total number of drugs worldwide: 60,000
Fewer than 500 characterized molecular targets
Potential targets : 5,000-10,000

8. Lots of stuff – not much information.
Some Numbers
Millions of entries in databases
CAS : 23 million
GeneBank : 5 million
Total number of drugs worldwide: 60,000
Fewer than 500 characterized molecular targets
Potential targets : 5,000-10,000
Lots of stuff – not much information.

9. Bioinformatics Chemoinformatics Protein Large databases
Small molecule drug
Large databases
Not all can be drugs
Large databases
Not all can be drug targets
Tropsha compares these. Let’s look at some of the comparisons he makes. Mutual similarity techniques.

10. Bioinformatics Chemoinformatics Protein Large databases
Small molecule drug
Large databases
Not all can be drugs
Opportunity for data mining techniques
Large databases
Not all can be drug targets
Opportunity for data mining techniques
Tropsha compares these. Let’s look at some of the comparisons he makes. Mutual similarity techniques.

11. Trends in Chemoinformatics
New methods need to establish QSAR for thousands of molecules
Database mining and pharmacophore searching techniques
Non-linear analytical methods applicable to large databases
Design of new molecules with drug-like properties rather than mere high-affinity ligands for existing targets.

12. Trends in Bioinformatics
Traditional: sequence to function
New thought: structure to function. (Same structure – different sequences; Structure more conserved than sequence.)

13. Vision: Integration of Chemoinformatics and Bioinformatics
CADD: computer-aided drug discovery (instead of computer-aided drug design)
“Start with a gene sequence and using computational procedures design a molecule capable of affecting the activity of this gene or its product”

14. Questions?
Once a scientist find thousands of potentially interacting molecules/proteins … then what?
Proof of concept?