crolltristan.bsky.social
Structural biologist and lover of all things biochemistry. Principal Scientist at Altos Labs. Developer of ISOLDE for macromolecular modelling in cryo-EM and Xtal maps: https://tristanic.github.io/isolde/
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“What is biology?”
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This brings back memories… climbing at Mt Arapiles, near the top-out about 30m off the ground I came across a crack very like this, with an odd white spot deep inside. Got closer to look, and realised it was a teeny tiny pair of fangs… unforgettable moment.
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I’m guessing your problem is the dependency on the “sanity” package. Unfortunately that stopped being maintained a while back, and won’t install in the latest Python version.
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🎶 When a muppet with teef finds a home on the reef, that’s a moray 🎵
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(this is actually the old laptop I used for most of my original work on ISOLDE. Poor little thing… will try to look after it better in future)
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Lady Cassandra??
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Could of course fire up a “proper” docking package for that, but often this way seems quicker and easier (and helps get a better feel for the site, to boot). Take out the map, “isolde restrain distances” to maintain local conformation, then just play with it.
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Both true. :) Although if it’s a novel ligand (or just something not in the CCD) the first point isn’t such a big issue. I don’t use it *that* often, but I do occasionally use it quickly assess hypotheses (“I wonder if{ligand} might plausibly fit this pocket?”).
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Still trying to work that out, I’m afraid. While we have some interesting “ISOLDE-adjacent” stuff in the works, my day job currently doesn’t leave a lot of (well… any, really) time free for development of ISOLDE itself. Exploring options to support it in a more sustainable way.
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One nice quality-of-life addition: all “open” commands now have an optional “cofr” argument. So for example…
open ligand.mol2 center cofr
or
open {smiles string} from smiles center cofr
… will put the ligand on ISOLDE’s crosshairs ready to move around and merge in.
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While I haven’t had a chance to add anything really substantial to ISOLDE, the @www.cgl.ucsf.edu team have added a bunch of great new stuff to ChimeraX itself.
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For people who managed to install older versions of ISOLDE into ChimeraX and found they promptly failed… sorry, that’s my fault. I didn’t RTFM about Python’s ‘~=‘ specifier. Thought “~=1.8.rc0” meant “>=1.8.rc0”, ==1.8.* when it actually means “>=1.8.rc0, ==1.*”.
🙃
Anyway, update to fix.
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I’m afraid I honestly don’t remember that. 🤷♂️
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I remember Jane Richardson and her team doing a fair bit of work trying to sort out “total junk” from “partially correct” down in the very-low-pLDDT regime. Don’t know if/where it was published, though.
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Came to the comments looking for exactly this.
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Huh. That’s interesting to know. Same root cause, I guess… if you were to calculate the conformational energy it’d be utterly horrific… but because it’s (more-or-less) symmetrical it can be surprisingly stable. Nice edge case showing limitations of classical restraints.
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One of the reasons I introduced adjustable nonbonded force strength in ISOLDE (the bigger one being that with “vanilla” Lennard-Jones forces would go out of range leaving the minimiser with no gradients to follow). Makes these easy to escape these days - turn down til it pops out, then turn back up.
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Heh. I see these sorts of “accidental rotaxanes” show up occasionally. Usually (only?) when some form of MD fitting was used - the VDW force is vastly stronger than bonds at short distances, so bad clashes involving rings sometimes end up in this weird metastable arrangement.
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I’m guessing she was blotting for TREX-1?
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Yeah… I figured that would be the case.
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That’s fair.
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Yep - I’m looking forward to that too.
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Thank you! Glad I finally took the plunge.
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Thanks!
Finally decided that other place was getting too depressingly dystopian (Dead Internet Theory, anyone?). Gotta say this all looks quite nice!