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Dan Erlanson, who needs no introduction in this forum, commented on the previous post. I have to agree with him that the Hann complexity model is not easy to apply in practice. It predicts that there will be an optimum level of complexity for a given assay system (detection technology + target) but doesn’t really tell us where a specific combination of molecule and assay system sits relative to the optimum.
Screening library design, as Dan correctly points out, involves striking a balance. One needs to think a bit about screening technology and the likely number of compounds that you’ll be screening. Another consideration is whether the screening library is generic or directed at specific targets or target families. I’m very interested in screening library design and expect to post on this topic in the future.
Dan notes that low complexity molecules often don’t find favour with medicinal chemists and I‘ve experienced this as well. Having structural information available gives us confidence to do something other than what a former MedChem colleague called ‘pretty vanilla chemistry’. Put another way, to make the most of the output from fragment screening, the medicinal chemist needs to be seeing a phenyl group as a synthetic handle