I'm trying to compare the 3D distance between two AAs with their evolutionary conservation. However, I'm coming across a problem when looking for 3D crystal structures of HIV-1 proteins ... mainly that the majority of crystal structures of proteins are from experiments where the protein of interest is bound with active site inhibitors. Here are some examples for reference:
I'm not incredibly familiar with 3D structures but I do know that these are small-molecule inhibitors. Can I assume the majority of the structure is unchanged? Should I take many different structures of the protein (with different SMIs) and average them somehow?
I know that all of these methods will add plenty of noise to the distance measurements but I'm just looking for a "back of the envelope" calculation for an initial hypothesis test. Do you think this will add too much noise to the see any signal? If so, can you propose another idea?