This seems to understate the challenge and power of generating good hypotheses.
This seems to understate the challenge and power of generating good hypotheses.
Let's say you want to know which residues in a protein are important for a particular function, so you can tweak them to improve function.
You could
- spend months or years solving a structure of the complex then look at the structure and look at the direct contacts - then mutate to various other resides to see if they affect function ( finding out that even with a structure of the complex your chosen list is far from 100% correct )
- look at sequence alignments and then make a library of millions of variants and screen in a couple of months.
The first feels better as the glorious scientist is doing 'rational design', however it can be much more hit and miss and slower and more expensive.
As I understand it, one of the things about Cryo-EM is it's potentially much faster/easier than previous methods - but even so, looking at the structure doesn't get you to the answer direct - it's still very much hit and miss.