First principles

[Vanuan]

Rough idea, might be not precise:

• Once there was no life. There was just inanimate matter, molecules flying everywhere.
• Organic matter formed into nucleic acids
  • The first organic compounds were formed during some physical/chemical reaction. Organic means "anything containing carbon" (C). All organic compounds expect CO2 also contain Hydrogen (H)
  • Nitrogenous bases (nucleobases) were formed, meaning organic molecules containing Nitrogen (N). They also contain Oxygen (O)
  • 5 nucleobases are the most common - adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U), though there are other
  • Nucleobases bonded into pairs by hydrogen bonds
  • Nucleobases formed into nucleosides (binding with a 5-carbon sugar - ribose or a desoxyribose)
  • Nucleosides formed into nucleotides (binding with a phosphate group)
  • Nucleotides and base pairs formed into nucleic acids - RNA and DNA
• Nucleic acids transformation
  • There was a variety of nucleic acids
  • Some nucleic acids were able to catalyze a reaction. Those are called Ribosomal ribonucleic acid (rRNA) or rybozymes
  • Some rRNA are able to cut themselves (self-splicing)
  • The messenger RNA (mRNA) were formed. Those are RNAs that are cut in half and used as a template to produce a protein
  • mRNA can't produce a protein themselves, a small adapter molecule, tRNA is used as a temporary link between mRNA and amino-acid sequence of proteins
  • rRNA with ribosomal proteins form a ribosome
  • at some point a proto-cell was formed: there was a primary transcript RNA which could produce mRNAs, tRNAs and rRNAs, there was a cytoplasm (a soup of water, salts and proteins), there were ribosomes which could produce proteins
  • 
• Cell sophistication
  • at some point a lot of proteins were produced around a nucleic acid - a membrane was formed
  • if a membrane is formed around nucleic acid, it is considered a virus, if a membrane is formed around nucleic acid with water, salts, ribosomes and other stuff, it is called a bacteria or archaea (prokaryote)
  • some time later another type of membrane was formed from chromosomes (many DNA molecules) - nuclear envelope with nuclear pores. Along with mitochondria, ribosomes and cell membrane they formed a first eukaryote.
• Evolution
  • RNA transcription can be erroneous - a mutation happens
  • some mutations are beneficial, some are harmful. Beneficial are those which allows organisms to reproduce
  • eukaryotes exploded into protozoa, fungi, plant, and animal organisms

[Vanuan]

So, to understand how coronavirus works these are the questions

• how it attaches to the living organism
  • how it goes through cell membrane (cell receptors)
  • how it deactivates defense mechanisms
  • how it reproduces itself
  • how it produces proteins
• how it affects the living organism
  • how it affects proteins
  • how it affects cells
  • how it affects tissues
  • what are the symptoms

There are the following instruments:

• real biological experiments
  • atomic probe microscopy
  • optical microscopy
  • mice observations
  • clinical trials
• biological simulation/modeling
  • molecular dynamics (atoms and molecules)
  • Brownian dynamics (cells)
  • reaction-diffusion master equation (multiple cells)
  • whole body model (Human Cell Atlas)

After that, we can take on the interesting part:

• how to treat the decease (without harming the living organism)
  • how prevent binding to cell receptors
  • how to stimulate defense mechanisms
  • how to prevent reproduction
  • how to block proteins produced
  • how to treat the damage already done

Of course, we can't wait until we have the computation power to build the whole body model (or until it becomes accurate enough), so scientists are taking shortcuts, sharing pieces of incomplete knowledge.

[Vanuan]

https://www.youtube.com/watch?v=nNK3u8uVG7o

[Vanuan]

Now, protein folding. There is a CASP project to assess protein modeling. Each 2 years there's a set of non-public experiment data which is used as a test dataset to asses prediction models. The latest one is CASP14 (2020). The dataset of the previous competition (CAPS13, 2018) is used to assess the next model.

The state of the art is the AlphaFold which won the CASP13 competition.