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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. Terminology Overview.
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Presentation of Recent Trends in Computer-aided Drug DiscoveryBy Alexander Tropsha Current Opinion in Drug Discovery & Development, 2000 Nancy Baker SILS Bioinformatics Seminar January 21, 2004
Terminology Overview • “ics” : genetics, genomics, proteomics, bioinformatics, chemoinformatics • Modifiers • Structural • Functional • Pharmaco • Informatics – general scientific discipline dealing with storage, analysis, and retrieval of information
Genetics Review DNA: TACGCTTCCGGATTCAA transcription RNA: AUGCGAAGGCCUAAGUU translation Amino Acids: PIRLMQTS Protein
Overview Continued –A simple example Protein Small molecule drug
Overview Continued –A simple example Protein Small molecule drug Protein Protein disabled … disease cured
Chemoinformatics Bioinformatics Protein Small molecule drug • Large databases • Large databases
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
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.
Chemoinformatics Bioinformatics Protein Small molecule drug • Large databases • Not all can be drugs • Large databases • Not all can be drug targets
Chemoinformatics Bioinformatics Protein 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
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.
Trends in Bioinformatics • Traditional: sequence to function • New thought: structure to function. (Same structure – different sequences; Structure more conserved than sequence.)
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”
Questions? • Once a scientist find thousands of potentially interacting molecules/proteins … then what? • Proof of concept?