@dakami on computational biochemistry for SARS-CoV-2 – electrostatic signatures under changing levels of acidity

Notes from the last time I nerded out with Dan Kaminsky

Dan’s death is a weird note on which to start my blog, but it’s also a good example of why I’ve been wanting to start one again. Facebook and Twitter are not ideal for writing linkable posts that go into some depth.

So, on the morning of Sep 19, 2020 I accidentally ran into a photo of him online, wrote to him and we had a nice catch-up. I’ve posted below the scientific parts of that conversation. I’m omitting my own parts, so you can safely read everything in Dan’s voice (except the parts in bold)

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Dan writes:

Spent the last six months working around the clock learning computational biochemistry. Intriguing field. Hated chemistry in high school but it seems to be the fundamental substrate at play here. At least that’s what the big compute jobs are showing.

…

Nature doesn’t need our help to come up with nasty viruses. Motivation is to figure out the actual deal with Covid. Because it’s not just the flu but we aren’t exactly dying like Wuhan either.

…

Hello fellow pressed into service Covid nerd :)

Bits of your space have shown up here. I didn’t know mutations were so much more common against Arginine and, to a lesser extent, Glycine.

…

It’s all pretty wild. https://tinyurl.com/dakami-field and https://tinyurl.com/dakami-thunderdome

My research is looking at electrostatic signatures under changing levels of acidity. I should see how the strains of Covid compare to each other.
Proteins and their aggregates are all basically steam engines powered by magnetically guided hydrogen flow.

It’s crazy, protonic computing

Hydrogen ions are protons, about 1800 times heavier than electrons, so they drag matter around as they move

That incompressibility of water is the system computing where to distribute the hydrogen pressure. You’re seeing the boundary conditions as the fields go positive or negative

closer views

something odd happens at pH (the H is in fact Hydrogen) of 5.5

it's this critical balance point all over the place

below 5.5, calcium is leeched from teeth (why you get cavities). on death, our bodies quickly rebalance to pH of 5.5. Most proteins have a balancing point of positive and negative fields around 5.5, which I'm working to quantify. You can see it visibly above, the even pair is at I think 5.4?

and that's at a 0.1 granularity

not all proteins, there's quite a bit of variation, but many, it keeps coming up

it's why i started looking at acidity, it kept being mentioned in all these contexts

when you realize acidity is hydrogen pressure a lot of things stop being mysterious

Anyway most of these behaviors are modeled under physiological ph of 7.4, but lung damage very quickly acidifies the entire airway to (again) 5.5 chronically and below 5 acutely

Yes [meaning just simulation, no empirical work –GL]

Amazon just sent me the confirmation

https://www.biorxiv.org/content/10.1101/2020.07.04.187989v1.full

experimental results confirming

there's an equivlanet paper for sars-cov-1

same balancing points as in the sims

i've got a few thousand proteins modeled, and i plan to compute against the entire PDB archive

[I talk about my own work a bit]

*nods* yeah, most interactions are surface interactions. one of the cooler things is it looks like sars-cov-2 swaps surfaces depending on acidity

at our scale of matter, two sheets of paper will not phase through each other

down there though

like, the hydrogen pressure pulls one surface out, pushes another one in, through each other

reality is porous down there

or i suppose i should say matter

porosity is the point though, it looks like we have this entire class of membrane transfer disorders

ore directly though, 1) we can detect airway acidification long before there's any apparent symptoms -- remember the first detections were accidental, just some lung cancer patients getting biopsies. also remember the mouth is part of the airway. saliva ph checks are easy. 2) we can correct airway acidity through various ways. it's not even off label, it's a thing we do in a variety of circumstances (rabies, another virus with uncomfortable neurological effects we use therapeutic coma for). 3) acidity might explain why it's difficult for the immune system to remember these virii, they simply have wildly different shapes *after* they've infected you.

if nothing else we should be checking all these treatments at the ph they're going to need to work at. and not assume blood speaks for all tissues

it's been a ride. trying to get this paper out of my head, trying to get the tooling up and running

streamlit is great if you haven't seen it

[transition to non-science topics]