Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.
Here’s a look from the D. E. Shaw research team at fragment binding, and even if you don’t do fragment-based drug discovery, it’s worth a read. That’s because the mechanisms by which fragments bind to proteins are most likely the fundamental ones by which larger molecules bind as well; this is the reductionist look at… Read More
We chemists would love to be able to do just a tiny bit less chemistry now and then and just let models and simulations tell us what would happen instead. Only every once in a while – you wouldn’t want to obtain such a perfectly accurate picture of chemical and physical interactions that there was… Read More
This new paper on “ultra-large” virtual screening is well worth a look in detail. We find a great many lead compounds in this business by random screening of compound libraries, and virtual screening is (as the name implies) the technique of doing this computationally instead of with hundreds (thousands) of sample plates and tireless ro… Read More
The results of the biannual CASP (Critical Assessment of Structure Prediction) effort have been released. This is a widely-watched competition between different groups (and different programs, methods, hardware, etc.) to see how well protein structures can be predicted de novo from just the protein sequences themselves. In the main category, the or… Read More
Let the machine learning wars commence! That’s my impression on reading over the situation I’m detailing today, at any rate. This one starts with this paper in Science, a joint effort by the Doyle group at Princeton and Merck, which used ML techniques to try to predict the success of Buchwald-Hartwig coupling reactions. The idea… Read More
I enjoyed this ACS Med. Chem. Letters perspective on AI and machine learning in medicinal chemistry. It has several good points to make, and it brought up one that I haven’t gone into here before: if you’re mining the literature, you will get what the literature can tell you. At the very best, the high… Read More
You hear medicinal chemists talking about the “magic methyl”, the big effect that a single CH3 group can have on potency or selectivity. Here’s a new J. Med. Chem. paper that shows one in action.That structure looks like a kinase inhibitor if anything ever did, and so it is. But small changes to it can… Read More
Peter Kenny has a paper out on ligand efficiency that’s required reading for medicinal chemists using (or thinking about) that concept as a design tool. I’d recommend reading it with this recent paper – between the two of them, you’re going to have references to a huge swath of the literature on how to measure… Read More
Here’s an example of something that we’re all going to see more of in the coming years: the computational approach to biochemical pathway discovery and (potentially) new therapies. In this case, the authors are looking at some pretty intractable tumor types (type 3 and type 4 medulloblastoma), which is a good place for discovery in… Read More
OK, the “Silicon Valley Meets Biotech” subject has come up around here numerous times, most recently here, about a startup out of YCombinator called Verge Genomics. But several people have called my attention to this proposal over at (yes) YCombinator, so by gosh, it’s coming up again. Because this is just too much to believe. Read More
