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.
Just how are things organized in a living cell? What’s next to what, in three dimensions? That is, of course, a really hard question to answer, but we’re going to have to be able to answer it in a lot of contexts (and at high resolution) if we’re ever going to understand what’s going on… Read More
Like many organic chemists, I find natural products very interesting, since their structures are often things that I would never imagine making (and in some cases have trouble imagining how to make at all!) But there’s a feature of the literature in that area that not everyone appreciates: the fact that a reasonable number of… Read More
When I first wrote about small-molecule structures obtained by microED (electron diffraction), I wondered if there were some way to get absolute stereochemistry out of the data (as you can with X-ray diffraction under the right conditions). Several groups have been working on just that problem, and this new paper now shows that it can… Read More
The number of stories and journal articles about how CRISPR DNA-editing technology works, has worked, and is planned to work are beyond counting. How about an article about how to stop it in its tracks? That’s this one, just published in Cell from a multicenter team in Cambridge and New York. It describes a screening… Read More
I had the chance yesterday to attend a one-day symposium on Cryo-EM (and MicroED) techniques here in Cambridge. The whole thing was co-hosted by ThermoFisher, whom I gather are having a glorious time selling these instruments and want to extoll their virtues as much as possible, and by MIT. It helps that there are a… Read More
This is a good brief overview of a topic that’s becoming more important all the time: analysis on the single-cell level. And as the authors mention, it’s partly a case of wanting to do this, and partly a case of there being no other choice. Larger pooled tissue samples just don’t have the level of… Read More
I suppose I deserve this one. Some years ago on the blog, I wrote about my days in grad school having to learn about symmetries and vibrational spectroscopy. Sparingly has that knowledge come in handy since then, but the course is still a vivid memory for me, since that’s the clearest example I had yet… Read More
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 spend a lot of time in this sort of work thinking about protein structures. Traditionally that’s been the province of X-ray crystallography, later joined by solution NMR, and more latterly by cryo-electron microscopy. Each of these has its own set of advantages and disadvantages, but one big split is between the solid phase (X-ray… Read More
Here’s something that many of us don’t tend to think about when we think about enzymes: vibrational energy. But it’s long been thought that anisotropic vibrational energy transfer (VET) plays a role in both enzyme active sites and in things like coupling to allosteric sites. Getting a handle on that, though, has not been easy… Read More
