The MD simulations in both enzymes revealed very stable substrate binding, via strong salt-bridge interactions of the guanidine moiety of Arginine (R, cf. Figure . 1) with the carboxylate ends of either substrate. In addition, as shown in Figure both simulations reveal the presence of a consistent water chain mediated by a heme-propionate (also see supplementary video VS1 and VS2 for water channel). The presence of a water molecule is considered to have an important function in peroxygenases. Therefore, our simulations for two important members of peroxygenase family show that peroxygenases may have evolved, during the primitive anaerobic conditions, in such a way that they preserved the proton transfer route (via heme propionate) while bypassing the other route (acid-alcohol pair).