3 ms·
"The four structures of AmpC determined with the new docking hits are available from the PDB with accession numbers 6DPZ, 6DPY, 6DPX and 6DPT." Are we in a sit
by roomey 8y ago
"The four structures of AmpC determined with the new docking hits are available from the PDB with accession numbers 6DPZ, 6DPY, 6DPX and 6DPT."
Are we in a situation now where, if I have a bad anti-botic resistant infection I can just order these molecules on the off chance that they will help me?
Can I order a toxin?
Or are these molecules just impractical to use outside of a lab setting
- fabian2k 8y agoThey only determined whether those specific molecules bind to the target. They didn't test if they are toxic, if they are able to actually get to the target, how stable they are under real conditions, into which metabolites they are processed in humans, ... This is the very first step towards developing potential drugs, it's very, very far from an actual drug. And drug development wasn't the goal of this paper anyway. And the idea behind this paper was to find molecules that aren't in any catalogue, so you would still have to synthesize them yourself or pay someone to do a custom synthesis for you.
- daddylonglegs 8y agoI thought the point of the library of molecules used was the supplier (Enamine) has a systematic method of synthesizing the molecules they've listed. It appears that, in practice, they can supply 90% of the molecules they offer, synthesized on demand: > Of the 589 molecules selected, 549 (93%) were successfully synthesized (Supplementary Table 10 and Supplementary Data 11, 13) I fully agree your main points.
- fabian2k 8y agoThat's still custom synthesis and not off-the-shelf compounds. No idea how expensive they are in this case.
- daddylonglegs 8y agoAbout $100 apparently: > Over the past decade, Kiev-based Enamine Ltd has innovated an efficient pipeline to produce any of over a billion never-before-made drug-like compounds on demand — at a cost of about $100 per molecule — by combining any of tens of thousands of standard chemical building blocks with one another using over a hundred established chemical reactions.
- justtopost 8y ago'Per molecule' gives no real indication of cost, that appears to be a 'tooling' charge, to design the reaction chain. I doubt $100 will buy you any useful quantity of any research chemical, much less a custom mfg one.
- semi-extrinsic 8y ago"Available from the PDB" means that you can download the molecular structure and view it on your computer. E.g. here is one of them: https://www.rcsb.org/structure/6DPZ https://www.rcsb.org/structure/6DPZ
- trott 8y ago> Are we in a situation now where, if I have a bad anti-botic resistant infection I can just order these molecules on the off chance that they will help me? Very far from it. I wrote a docking program myself (the most popular one, currently, I believe), and I get emails of this nature sometimes. Molecular docking only makes predictions about binding. Typically, this gives you what people call an "enrichment", i.e. your guesses are better than random, hopefully much more so. Still, most of these guesses are typically wrong. For example, you might go from 1 in 1000 odds to 1 in 10. When you do find a drug-like molecule that binds your chosen protein, this is only the beginning of the drug development effort that may end up costing billions.
- j-wags 8y agoHey Oleg, I just wanted to say thanks for doing some really great work. AutoDock Vina made a huge impact on the field, and its results are still on-par with commercial docking codes. Academic software development is a combination of some of the worst parts of open-source software development and the worst parts of academia, but projects like Vina motivated me to be a better coder and scientist in grad school.
- trott 8y agoThanks for the kind words!