Friday 7th June, 2013
3:45pm to 4:15pm
Reductionism is one of the most crucial thought processes.
It was a key method to separate the alpha and beta adrenoreceptor families (Ahlquist, Am. J. Physiol. (1948) 153:586), and deducing complementary ligand shape from solved crystal structure is a fundamental idea in structure-based virtual screening. However, it has also been questioned whether basic reductionism used in chemistry and physics is sufficient for discovery of new drugs (Maggiora, J. Comput.-Aided Mol. Des. (2011) 25:699). In the data made publicly available in recent years through projects such as ChEMBL, there is adequate evidence that the "one-target-one-drug" design assumption and expectation of single-target selectivity generally does not hold, and many compounds can be shown to be polypharmacological. This promiscuity needs to be evaluated from both the compound (Hu and Bajorath, Drug Discov. Today (2013) in press) and protein (Jalencas and Mestres, Med. Chem. Commun. (2013) 4:80) perspectives. When we consider the "many-to-many" perspective, it is perplexing to arrive at uniform rulesets or generalizations based on the large quantities of assay data available. In this talk, I will discuss some of these recent perspectives, share some personal analyses, and consider the question: are network-based approaches to chemical modulation at odds with reductionism, or are they complementary?
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