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so the alchemical transformations we looked at theyamp;#39;re awesome to calculate free energies cheaply the only problem is it did so along a leg where the end result was an unphysical state so i canamp;#39;t compare that to anything in experiment so letamp;#39;s go back a second and think about what we were after we were after the state when i have a protein in water and you can imagine that protein and being in the other room and then i had a ligand in water theyamp;#39;re not seeing each other theyamp;#39;re not interacting but then we go along a path here where it says delta g bind and the other state my target state is then going to be the protein that has the ligand bound and theyamp;#39;re all in water that is an expensive and difficult calculation to do and expensive not just expensive in terms of dollars but because itamp;#39;s expensive and difficult to do itamp;#39;s going to be noisy itamp;#39;s going to be a bad result and it will take a long time what i did on t