natechols

15 ms·

91.
by natechols 6y ago
I'm always fascinated in the assumptions underlying some of these proposals, and how little thought they've given to the problem. For example, the complete disregard for the lives or autonomy of the "replacement crew",
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by natechols 6y ago
Academic scientists can be intensely conservative, even reactionary, when confronted with new ideas and methods. If you want to see something really horrific, try digging up some of the original debate on whether experimental data depositi
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by natechols 6y ago
Oh absolutely, they picked a model system that is both very rigid and has extremely high internal symmetry, and I assume they did rotational averaging to use fewer images. But these ideal systems are very useful for determining the limitat
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by natechols 6y ago
Most of these still count as low-resolution - I don't see anything better than 3 Angstrom in the PDB, most are much worse. More than good enough for movies and functional assays, but some of the fine details will be guesses.
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by natechols 6y ago
The uncertainty also comes from averaging many images together. But yes, it's less than 1 Angstrom; the deposited structures (for example https://www.rcsb.org/structure/7A6A ) record atomic uncertainties, "B-
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by natechols 6y ago
It's absolutely useful for drug development and pharma companies appear to be getting heavily invested in the technique. The problem is that they've been trying to use structural biology this way for close to four decades now, an
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by natechols 6y ago
This is not far from the truth, except the detectors are actually relatively small (and very expensive), there's more aluminum foil than the Victorians used, and we have slightly better hair on average. The last time I used one of the
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by natechols 6y ago
Brute-forcing the problem with a variant library and high-throughput screening could easily end up being far more inefficient. At least with crystallography it's easy to set up the experiment, whether or not it actually works.
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by natechols 6y ago
It's also possible it's colored by uncertainty in the atomic positions - what crystallographers call the "B-factor".
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by natechols 6y ago
With hard xrays you can visualize interatomic densities and lone pairs. I know there are structures down to 0.5Å resolution now but that must have required careful setup. I've seen diffraction out to 0.75Å but I could never collect c
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by natechols 6y ago
I do not know what it's like in practice now, but on a purely theoretical basis, if you are trying to solve a completely novel structure with no known homologs, especially if it's something on the scale of a ribosome, direct imagi
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by natechols 6y ago
I think your criticism of structural biology can be applied to any methods-focused investigation, as opposed to biology-focused. I've certainly been down the "okay we have the data, what does it mean?" path more times than I
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by natechols 6y ago
You can still get artifacts due to freezing. But the lack of crystal packing makes it much easier to detect functional conformational changes in different copies of the molecule on an EM grid.
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by natechols 6y ago
Pedantic note: they're not really imaging individual atoms directly; it's a composite view of the structure based on averaging thousands of different images of copies of the molecule in different orientations. This is true of oth
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by natechols 6y ago
I take it you haven't met very many university research professors. (But I probably should have used the term "central planning" instead since that is much closer to what I meant - the problem of over-coordination when a mor
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by natechols 6y ago
You are assuming that the construction of the system has nothing to do with human nature in the first place. I think there are a lot of godawful perverse incentives embedded in our current system, and I suspect we could come up with a much
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by natechols 6y ago
Yeah, the good news is that everyone involved in the CRISPR discoveries has done extremely well both financially and scientifically, even if they're not getting a trip to Stockholm. It definitely shows the limits of the three-person-m
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by natechols 6y ago
People have been trying for well over a century now to form alternative institutions (including governments) based entirely on human cooperation rather than competition. The results have typically been less than impressive so far. Keep in
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by natechols 6y ago
Didn't Church's very similar paper come out at the same time as Zhang's?
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by natechols 6y ago
It wasn't just that, it was the entire hype machine. Lots of schadenfreude going around today. I probably would have preferred they split the CRISPR award across chemistry and medicine prizes, but life isn't fair.
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by natechols 6y ago
1) Because human beings aggressively pursue their self-interest, which extends to getting new credit for scientific discoveries. 2) Because scientific discovery often requires multiple competing approaches (because you don't know which
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by natechols 6y ago
I was wondering about this too - when I saw the title I assumed it was a molecular dynamics study.
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by natechols 6y ago
The supercomputer in this article is extremely specialized hardware design to maximize peak performance across all nodes. Using just a single CPU core to run a bioinformatics study would be like taking an army tank to drop the kids off at
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by natechols 6y ago
"Lower cost", I should have said. Skipping straight to Phase III helps.
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by natechols 6y ago
At least in the bay area the gap is enormous - and biotech is not known for paying poorly!
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by natechols 6y ago
There is a lot of nonsense tossed around about who actually discovers the majority of drugs and how the public sector can be more involved, but you've identified one case where government and academia could make a huge difference, e.g.
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by natechols 6y ago
We have actual Maoists in the bay area - they're a tiny faction and utterly irrelevant, but they're very good at getting attention and they like to poison the atmosphere for everyone. There are no Maoist governing parties in Euro
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by natechols 6y ago
What terrifies me even more is when the same tribalism leads people on either side to start reflexively defending their entire "side" - thus the right-wing fondness for Pinochet or Franco, or the left-wing fondness for Castro or M
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by natechols 6y ago
You're both applying a wildly subjective label whose meaning nobody can agree on. I happen to think (as a relatively centrist American living on the West Coast) that those opinions are indeed "centrist". They might count as
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by natechols 6y ago
How is the US style of center-liberalism extreme, as compared to an ideology that demands total control over the economy and its citizens? Or do you think concepts such as "rule of law" are extremist?

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