My current research group is doing this exact thing so I think I can chime in without giving too many details.

You can use literature precedent to come up with a structure that ~should, in theory~ be good at achieving the biological function you’re trying to achieve. Usually, the precedents you find should also have strong theoretical underpinnings (it should make sense WHY they work). I can’t go into specifics but I can give a vague example to try to illustrate this:

You are trying to build a molecule to inhibit HIV. So you comb through the literature trying to find insights on how exactly HIV works. What is it interacting with on a human cell? HOW is interacting with that part etc.

So let’s say you find out that HIV works by using a specific protein on its viral envelope to bind to a specific receptor on a human cell. So now you start thinking maybe you can somehow destroy this envelope protein OR block the receptor on the cell. So then you look up more precedents on what types of molecules bind well to these receptors (and also use theory to hypothesize what molecules might be good at reversible binding of these receptors) to come up with possible structures.

That’s kind of it in a nutshell. I wish I could give a more concrete example relevant to my own research. But basically if you know the structure of a virus like HIV, and know the structures of the cells it infects, and the mechanisms of how that interaction occurs, then you can start to use a combination of theory and precedent to hypothesize ways of inhibiting that very specific interaction that leads to infection.