Notes from hackernews discussion on AlphaFold

2024-07-29T05:39:33+00:00

You are basically made of proteins, which are basically folded sequences of amino acids, **proteins are molecular machines** that are the fundamental building block of animals, plants, bacteria, fungi, viruses etc.

This comment https://news.ycombinator.com/item?id=32264898 led to a discussion which helped me learn a lot.

you see these 3D representations of specific proteins as a crumple of ribbons I understand that proteins are huge organic molecules composed of thousands of atoms, right? Their special capabilities arise from their structure/shape. So basically the molecule contorts itself to a low energy state which could be very complex but **which enables it to "bind?"** to other molecules expressly because of this special shape and do the special things that proteins do-- that form the basis of living things. Hence the efforts, like Alphafold, to compute what these shapes are for any given protein molecule.

But what does one "do" with such 3D shapes?

• The ribbons and helices you see in those pictures are abstract representations of the underlying positions of specific arrangements of carbon atoms along the backbone.
• protein structures have a long history of being used in drug discovery
• BINDING SITES
  • The thing to understand is that proteins form "binding sites": areas that are more likely to attract other particular regions of proteins or other molecules, or even atoms. (https://news.ycombinator.com/item?id=32265157)
  • Think about hemoglobin. The reason it holds onto oxygen atoms is because it has binding sites.
  • Binding sites allow molecules to do things like temporarily attach to each other and let each other go under certain circumstances
• Different regions of the protein have different sequences of amino acids
• Protiens are big molecules made of atoms
• Drugs are small molecules that are designed to help or interfere with the operation of proteins instead.
  • Protiens are better called biologics.
• proteins are the machinery of the cell. They perform an immense array of functions and they must fold in a certain way to perform these functions. This is part of what's known as the structure-function relationship. https://news.ycombinator.com/item?id=32262856
• Can someone put AlphaFold's problem space into perspective for me? - more

If we knew:

(a) the structure of every protein (what DeepMind is doing here)

(b) how different protein structures interact (i.e. protein complexes - DeepMind is working on this but not there yet)

Then we could use those two building blocks to design new proteins (drugs) that do what we want. If we solve those two problems with very high accuracy, we can also reduce the time it takes to go from starting a drug discovery programme to approved medicine.