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by higginsc
2687 days ago
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I have been out of this space for a few years (transitioned to data science from drug discovery), but from my time doing in silico and in vitro work, a major issue with docking was rank ordering. His comments are right on the mark IMO. Especially this paragraph: >Another point is that high-middle-low effort on the D4 case. The binding assay results compared to the docking scores are shown at right. You can see that the number of potent compounds (better than 50% displacement, below that dashed line) decreases as the scores get worse; the lowest bin doesn’t have any at all. But at the same time, there are a few false-negative outliers with binding activity at pretty low scores, and at the other end of the scale, the top three bins look basically undistinguishable. So the broad strokes are there, but the details are of course smeared out a bit. These methods can filter millions of compounds down to hundreds, but as an academic lab, it's still a herculean effort to synthesize hundreds of compounds. And out of those hundreds, you might get a couple that are active. This study is a combination hard work, yes, but also a lot of money and luck. That being said, good for the team, and good for science. I have nothing but respect for Shoichet and Roth. Didn't ever cross paths with Irwin. |
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This makes me laugh since Shoichet was childhood friends with Irwin and they've worked together on almost everything together since 2000 when Irwin went to Northwestern to join his lab.