Abstract: | The active site of aspartyl proteinases (Asp) was modelled as two formiates connected with a proton and set in geometry corresponding to Asp 32 and Asp 215 side chain carboxylate groups of endothiapepsin. The shared solvent molecule was alternatively H2O and H3O+. Their positions and those of hydrogen-bonded protons were optimized using the STO-3G basis set. Full geometry optimizations were made of the hydrogen diformiate complexes with H2O and H3O+. Asymmetric hydrogen-bonded structures resulted from these calculations, except for the fully optimized complex with H2O. In the complexes with H3O+, one proton moved consistently to the proximate carboxylic oxygen yielding a neutral, hydrated formic acid dimer. Interaction energies and proton potential energy curves were calculated using the 4-31G basis set. The interaction energy with H2O was found to be 20.49 kcal mol?1 and 202.75 kcal mol?1 with H3O+. |