Ab Initio Molecular Orbital Studies on the Active Site of Papain

Ab initio molecular orbital calcuiations using a contracted basis of gaussian orbitals on the system methanethiol/imidazole are reported. For the hydrogen bond S---H---N in this system, which was chosen as a model for the active site of papain, a double-well potential was found at a S-N separation of 3.35 Å. This sustains a newly proposed mechanism for the catalytic action of papain which involves the existence of an ion pair ImH+-S-. From minimal basis set calculations on the system methanethiol/imidazole/formaldehyde an estimate is obtained for the stabilization of the first model by the hydrogen bond between imidazole and formaldehyde. In the latter calculations the total energy as a function of proton positions did not show double-well character. The stabilization energy tends to reinforce the shape of the potential as obtained in the former calculations. We conclude, however, that minimal basis set calculations are inadequate to elucidate the type of mechanism we are dealing with here.