receptor-ligand binding experiments?

[chef]

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let's say I want to find out where ligand X binds to receptor Y. the sequences of both are known, and recombinant proteins are amply available.

what is the most reasonable approach to get the answer? site-directed mutagenesis analysis?

also, is it more useful to find out the binding domain on the receptor, or the ligand, if the goal is to eventually develop new drugs that mimic the endogenous ligand??