In order to investigate the interactions of compounds with MATE1 further, we scrutinized the noninhibitor compounds which are known as in vitro typical substrates in FDA guidance 10 , 1-methyl-4-phenylpyridinium, tetraethylammonium, creatinine, metformin. The contacted amino-acids with these substrates were Gln49, Glu273, Trp274, Tyr277, Tyr299, Ala302, Ile303, Tyr306, Met307, Glu389. Since most of these amino-acids (Gln49, Trp274, Tyr277, Tyr299, Ile303, Tyr306) were the same with the inhibitor contacting amino-acids, we can conclude that substrate and inhibitor overall share rather similar binding space in MATE1. From the viewpoint of drug discovery using in silico technology, this indicates the difficulty to distinguish between classes based on the docking position, and this leads to the low predictivity of MM-GBSA score. On the other hand, from the viewpoint of drug discovery using experimental science, this is consistent with the fact that the IC50 values of each inhibitor when using different substrates are similar ; and practically this can release the experimental scientists from bothering of selecting substrates for MATE1.