Molecular Modelling for COVID

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Andreas "Mega" Stuermer

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Apr 1, 2020, 12:35:44 PM4/1/20
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Hi everyone - 

A friend asked me for a simulation to see if the drug methaqualone will bind to the SARS-entry receptor ACE2. 

Does anyone have a lot of experience in molecular modelling to predict binding? 

I feel the way I would do this would be dilletantic. 


Would love to hear your feedback 

Cathal Garvey

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Apr 1, 2020, 2:38:34 PM4/1/20
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Something to watch is that ACE2 is, as I understand it, not a receptor. It's a cell surface enzyme that acts on some pretty important hormones involved in blood pressure and kidney function.

So, something that binds the ACE family of proteins might run a risk of causing unintended side effects.

On the other hand, something designed to bind the viral spike proteins is probably less likely to accidentally bind those hormones, so I imagine it's a safer route for drug development. But I wouldn't know with much confidence, it's not my area. :)
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Sean Rowshandel

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Apr 1, 2020, 3:03:54 PM4/1/20
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This is a dangerous drug so no wonder you used the word dilletantic because it describes your friend

Cathal Garvey

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Apr 1, 2020, 3:04:53 PM4/1/20
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"Your friend" sounds a bit accusatory, why the hostility?

Andreas "Mega" Stuermer

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Apr 1, 2020, 3:27:14 PM4/1/20
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Ok, interesting. Thanks for the reply. 

Right now this is just discussing ideas forward and backwards. 

He says in "methaqualone hotspots" (it indeed seems to be an illegal drug) they would have the lowest COVID cases, and wondered if there's more than correlation. 

Haven't verified most of his claims yet, so I wanted to share and discuss with some of the smartest people I know - if there's any reason to believe this is worthy of investigation

Andreas "Mega" Stuermer

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Apr 1, 2020, 3:28:32 PM4/1/20
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Although, even if it would block the ACE2 for the Coronavirus, hormonal effects could make it unusable








On Wednesday, April 1, 2020 at 6:35:44 PM UTC+2, Andreas "Mega" Stuermer wrote:

Sean Rowshandel

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Apr 1, 2020, 3:34:34 PM4/1/20
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He's using him. You don't understand what this acquaintance asked him to do, clearly, and are putting salt on the wound. That drug isn't even on the market anymore. Even if it blocked the spread of covid-19 if you take enough to COMPLETELY saturate ace-2 and it didn't kill you, if it even binds to ace-2 at all (which I haven't taken the time to look up), it's not on the table. The person either is smart enough to know he's making fun of him, or just a regular old liability to society.

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cathal...@cathalgarvey.me

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Apr 1, 2020, 3:38:23 PM4/1/20
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That's assuming a lot and injecting unnecessary hostility into an academic query. If barbituate-type drugs or GABA -affecting drugs actually did have an effect, it wouldn't really matter whether the drugs themselves were still available: the question would be "why", and the answer to that might lead to useful solutions that had nothing to do with barbituates or GABA.

My guess would be that it's a spurious correlation and that given the difficulty of simulating binding efficiencies, it's not worth pursuing at the molecular/computational level until more research is done into the real-world observations. But discarding a query by speculating about malicious intent where there's really no evidence of same..isn't helpful.

Andreas "Mega" Stuermer

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Apr 1, 2020, 3:45:05 PM4/1/20
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Ok I have no idea how that escalated so quickly.

There's a guy, somebody who studied chemistry but doesn't work in the field, who read that a drug binds to the viral entry receptor. Or might have found an article on said correlation.

He asked someone who is more in biology if he knows how to do computer simulation on this.

Doesn't seem to sketchy to me, what are you suggesting his evil masterplan is?

Sean Rowshandel

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Apr 1, 2020, 3:58:22 PM4/1/20
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Not my problem

cathal...@cathalgarvey.me

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Apr 1, 2020, 4:03:02 PM4/1/20
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OK, but if you're not here to talk DIYbio and just like verbally abusing people, there are better forums for that.

Sean Rowshandel

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Apr 1, 2020, 4:05:39 PM4/1/20
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Thanks for illustrating why I spoke up

Sean Rowshandel

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Apr 1, 2020, 4:07:01 PM4/1/20
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I tried to unsubscribe last week but this made me sincerely upset to read

On Apr 1, 2020, at 4:03 PM, cathal...@cathalgarvey.me wrote:

Andreas "Mega" Stuermer

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Apr 1, 2020, 4:08:50 PM4/1/20
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I still don't get what you are saying, but maybe that's ok.

Just for your peace of mind, I wouldn't even know where to buy that drug and I'm not even interested to do that in a DIYbio setting if it's a regulated substance.

Take care.

Sean Rowshandel

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Apr 1, 2020, 4:14:16 PM4/1/20
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Appreciate it. Fyi it was deemed too dangerous back before seatbelts were required.

Bryan Jones

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Apr 1, 2020, 11:26:22 PM4/1/20
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If you want to look at potential binding, there are numerous protein docking software choices, my favorite is SwissDock. It has a nice, fairly simple web interface. You need to provide the protein structure file and the small-molecule ligand (inhibitor) structure file. There are some databases for lots of small molecules and there are ways to make your own. For the protein structure, you can download the *.pdb file from the Protein Data Bank, for example, one high-resolution model of ACE2 is 1R42. SwissDock will give you various possibilities of where the small molecule could bind. You can view the poses with software like PyMol (PyMol paid/trial version or get it for free by compiling the source code).
--Bryan Jones


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Claudio Tiecher

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Apr 10, 2020, 8:30:56 AM4/10/20
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Also another software available to visualize 3D biological structures is Chimera (https://www.cgl.ucsf.edu/chimera/).
Good luck,
Claudio

On Thursday, April 2, 2020 at 5:26:22 AM UTC+2, Bryan Jones wrote:
If you want to look at potential binding, there are numerous protein docking software choices, my favorite is SwissDock. It has a nice, fairly simple web interface. You need to provide the protein structure file and the small-molecule ligand (inhibitor) structure file. There are some databases for lots of small molecules and there are ways to make your own. For the protein structure, you can download the *.pdb file from the Protein Data Bank, for example, one high-resolution model of ACE2 is 1R42. SwissDock will give you various possibilities of where the small molecule could bind. You can view the poses with software like PyMol (PyMol paid/trial version or get it for free by compiling the source code).
--Bryan Jones


On Wed, Apr 1, 2020 at 3:14 PM Sean Rowshandel <rowsha...@mymail.vcu.edu> wrote:
Appreciate it. Fyi it was deemed too dangerous back before seatbelts were required.

On Apr 1, 2020, at 4:09 PM, "Andreas "Mega" Stuermer" <andreas....@gmail.com> wrote:
I still don't get what you are saying, but maybe that's ok. 

Just for your peace of mind, I wouldn't even know where to buy that drug and I'm not even interested to do that in a DIYbio setting if it's a regulated substance. 

Take care.

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