Politics of life

[Edward Montague]

Sometimes I wonder if our health is a political pawn .

Consider, for instance, the implications of an effective treatment
for cancer. Might this be perceived in various circles as a diminishing of the nuclear deterrent.
A strategic advantage if one group had this whilst another didn't.

At the very personal level, which many of us seldom approach,
politics and the machinations of those who have a contrary agenda
to your well being are the last things you want to confront.

Few might be aware of this; some decades ago the WHO were
promoting measures to curb the world's population.
A disaster, especially for the worlds unacknowledged minorities.

Now imagine an individual from this minority, how difficult is it
going to be to aspire to life extension in the sense that we're considering this.

Anyway a bit of reality and a bit of paranoia.

[sciw...@gmail.com]

This does seem to be related.

Today I was watching flying videos on youtube.
I was interested in the instrumentation in today's aircraft, mostly computerized.
The pilot relies upon these to chart a safe course through weather, his journey, aircraft parameters.
This is all necessary for a safe flight, autopilot is .available once the correct circumstances have
been establihed.

If only genomics,, protein assembly, drug discovery was presented in a similarly comprehensible
and interactive manner, especially considering that lives depend upon this too.

[sciw...@gmail.com]

Concerning Alphafold 2.

This is considered an advance in protein folding prediction
by many.

https://www.nature.com/articles/d41586-020-03348-4


Some however say that the intervening steps in the
folding need to be made apparent, in an accurate manner.

From
https://geneonline.news/en/2020/12/11/spotlight-alphafold-maybe-this-centurys-biggest-breakthrough-in-computational-biology/

"The predicted structure from AlphaFold2 is a snapshot of the protein’s
conformation, much like a crystal structure and not dynamic modeling of
the protein folding."


The latter is usually the domain of the standard computational
molecular dynamics.


Understanding an intervening configuration of the Covid 19 virus
spike was crucial in the development of a vaccine.

https://pubs.acs.org/doi/10.1021/acs.jpcb.0c03716#


Computational Molecular Dynamics continues to be limited by the
available hardware, especially when modelling large molecular
complexes.

https://par.nsf.gov/servlets/purl/10100859

All of this initially appears to be a software issue, whereby
we merge different approaches and cross reference the results,
or train a larger system that utilizes different modules.

The code for Alphafold 2 is yet to be made publicly available.




General Reference

Folding
https://www.hpcwire.com/2020/10/14/how-foldinghome-identified-and-visualized-sars-cov-2s-weak-spots/
https://www.nature.com/articles/s41401-020-0485-4


https://towardsdatascience.com/alphafold-2-explained-a-semi-deep-dive-fa7618c1a7f6
http://occamstypewriter.org/scurry/2020/12/02/no-deepmind-has-not-solved-protein-folding/

CMD
https://ieeexplore.ieee.org/document/6375578
https://iopscience.iop.org/article/10.1088/1742-6596/180/1/012028/pdf
https://www.hpcwire.com/2020/07/15/heffte-highly-efficient-fft-for-exascale/

Folding
https://www.blopig.com/blog/2020/12/casp14-what-google-deepminds-alphafold-2-really-achieved-and-what-it-means-for-protein-folding-biology-and-bioinformatics/
https://www.skynettoday.com/briefs/alphafold2

[sciw...@gmail.com]

> > been established.

> >
> > If only genomics,, protein assembly, drug discovery was presented in a similarly comprehensible
> > and interactive manner, especially considering that lives depend upon this too.

Jan 29 2021

Yet to be substantiated .

https://cen.acs.org/physical-chemistry/protein-folding/DeepMind-AI-predicts-protein-structures/98/web/2020/12

https://scitechdaily.com/major-scientific-advance-deepmind-ai-alphafold-solves-50-year-old-grand-challenge-of-protein-structure-prediction/

from
https://www.newscientist.com/article/2261156-deepminds-ai-biologist-can-decipher-secrets-of-the-machinery-of-life/

"
Lupas thinks for the next few years researchers will still need to do
some experimental work to check shape predictions, but will
eventually be able to rely on computation alone.
This will make a huge difference, he says, but the real revolution
will come from being able to use computers to predict how proteins
interact with other molecules.
"

from
https://youtu.be/ShQgQbnX-Ko?list=PL3lZhmfYpIKuPyW945016C78YmictCOTK&t=4

Distinguished Speaker Seminar Series, episode 1: The revolution
in protein structure prediction .

" lipid protein and other complicated interactions considered
ameanable to the techniques used in alphafold 2 "


Read more:

https://www.newscientist.com/article/2261156-deepminds-ai-biologist-can-decipher-secrets-of-the-machinery-of-life/#ixzz6kumrx8ER




Another consideration, utilize what nature has developed.

https://www.eb.tuebingen.mpg.de/protein-evolution/

Watch the video.

[sciw...@gmail.com]

Using a neural network to identify regulatory activity of
the genome .


https://www.sciencedaily.com/releases/2021/02/210218151102.htm
https://github.com/kundajelab/bpnet/

Pypi package

https://pypi.org/project/bpnet/ ?
https://pypi.org/project/bpnet-lite/

[sciw...@gmail.com]

Of note

Exosomes

pubmed.ncbi.nlm.nih.gov/32759948

There are other factors that are known and have yet to be
addressed.

The late Joshua Lederberg, former president of the New York Academy of Sciences, and Nobel
recipient, was well aware of Exosomes; many decades ago.

[sciw...@gmail.com]

These Exosomes can be separate from the normal genetic material of the cell, yet interact with the DNA, and most likely RNA, of the cell.
From the link presented you're able to determine that Exosomes can also be encapsulated.

Some Exosomes have a circular DNA structure and undergo rapid mutation, promoting further
cancerous growth; just as well someones seeking an assay and remedy.

Exosomes are different than Exomes .
Exomes are related to the Exons of the cells natural DNA.

Joshua Lederberg was also interested in Proteomics; I have a brochure from NYAS on the topic, that they published when they and Joshua were beginning this project.

[sciw...@gmail.com]

On Sunday, April 18, 2021 at 2:31:19 PM UTC+12, sciw...@gmail.com wrote:


Exosomes
pubmed.ncbi.nlm.nih.gov/32759948

Another link on a similar topic,

https://www.the-scientist.com/features/cancer-may-be-driven-by-dna-outside-of-chromosomes-68590

[sciw...@gmail.com]

Examining immune response, in the lab, before applying therapy.


https://www.researchgate.net/publication/323528075_In_vitro_immunotherapy_potency_assays_using_real-time_cell_analysis

[sciw...@gmail.com]

I'm attempting to piece together how drug discovery happens.
This is by no means comprehensive, or necessarily precise; at this time.

target drug

configuration
determined
by x-ray diffraction,
cyro-em and/or
protein folding
software.
__________________
protein <-- docking ----- ligand, possibly a protein too. | repeat
| |
| <-------------------------

energy , some measure of goodness of fit,
nowadays also determined through software .

[sciw...@gmail.com]

Attachment ?

[sciw...@gmail.com]

An edited version, to make everything more comprehensible.

Target molecule, usually a protein .

Configuration determined by x-ray diffraction, cyro-em and/or protein
folding software.

Large databases exist for the known molecules.

--------

Drug

Ligand, possibly a protein too.

Very large databases exist for the known molecules.
Using known drugs we're also able to use other information, like the toxicity
to humans.

--------

Docking, where we determine how well the drug binds to the target protein.
The energy released during docking is one measure of goodness of fit,

nowadays also determined through software .

The docking evaluation might be repeated numerous times, the structure of
the drug being tweaked every so often. Also different drugs are likely to be
evaluated.

-----------

Vaccines utilizing mRNA also require information from this methodology,
especially the sequence of events involved in protein folding.