Timeline for How to select the best ligands in a virtual screening matrix
Current License: CC BY-SA 4.0
12 events
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| Sep 2, 2022 at 13:34 | comment | added | Matteo Ferla | Ah. 28k is more than I thought. I find natural compounds awesome to stare at to see their biosynthesis, but I'd worry the routes for expansions may be more isolated than the modular building block approach —say you have a cyclised sesquiterpene (farnesol (3x isoprene) is 222 Da) and you would like to change a substituent it would need to exist in nature or on sale or easily modifiable (Codexis & co. sell plates of exciting enzymes but AFIK that is for production optimisation not exploration). | |
| Sep 2, 2022 at 11:53 | comment | added | albertr | What I did was to keep any ZINC "natural-products" entry also described as "for-sale", which (in theory...) should be available for buying from distributors, and also discard any that violated 2 or more Lipinski's rules. But yeah, still it left with around 28000 compounds. I will try to see if I can use LE without boosting the "very" small compounds. | |
| Sep 2, 2022 at 11:40 | comment | added | Matteo Ferla | My comment was about cost and success rate: smaller compounds are cheaper and more likely to be true so LE + a lower cutoff of 150–200 Da depending on the assay or co-crystal soak. So generally smaller compound hits are elaborated upon until one has a lead and jumping to the final product is a waste of cash. ZINC natural products is not make-on-demand & may require a chemist to source the plant (read: import paperwork) and extract the product (read: low yield). Plus they may not be not "drug-like" (cf. Lipinski's Ro5 vs. nature's proclivity towards PO4, CoA or glycosyl groups as a handle). | |
| Sep 2, 2022 at 11:04 | comment | added | albertr | Sorry Matteo I don't know where my comment went either! I used the ZINC database of natural compounds here, with the aim of drug discovery. It is expected to find things like urea I guess, and of course any result like this would be manually curated | |
| Sep 2, 2022 at 10:46 | comment | added | Matteo Ferla | I seem to have glitched the system by adding an extra comment and my previous comment has shrunk. If it's for drug discovery I'll re type it... :shrung: | |
| Sep 2, 2022 at 10:44 | comment | added | Matteo Ferla | If it is to find the native ligand of an enzyme, the task is completely different, but the monetary aspect is worse —say the native ligand is something like phosphoribosyl pyrophosphate and you have 10 candidates that are close, that will cost as much as the GDP of a small state. Therefore ancillary checks are needed like operon guilty-by-association etc. | |
| Sep 2, 2022 at 10:43 | history | edited | gringer♦ | CC BY-SA 4.0 |
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| Sep 2, 2022 at 10:37 | comment | added | Matteo Ferla | Urea?! —what dataset are you docking and what's the application? I had assumed it was Enamine REAL or Wuxi biologics dataset for purchasing for drug discovery. | |
| Sep 1, 2022 at 11:40 | history | edited | albertr | CC BY-SA 4.0 |
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| Sep 1, 2022 at 11:34 | history | edited | albertr | CC BY-SA 4.0 |
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| S Sep 1, 2022 at 11:25 | review | First questions | |||
| Sep 1, 2022 at 12:16 | |||||
| S Sep 1, 2022 at 11:25 | history | asked | albertr | CC BY-SA 4.0 |