I think the various contributors to the invention of the steam engine had a good idea of what they were trying to do and how their idea would physically work. Wikipedia lists the prerequisites as the concepts of a vacuum and pressure, methods for creating a vacuum and generating steam, and the piston and cylinder.

That's not too different from the alpha fold people knowing that there's a sequence to sequence translation, that an enormous number of cross-talk happens between the parts of the molecule, that if you get the potential fields just right, it'll fold in the way nature intended. They're not just blindly fiddling with a bunch of levers. What they don't know is the individual detailed interactions going on and how to approximate them with analytical equations.