Theoretical investigations of structure and enzymatic mechanisms of aspartyl proteinases: Part I. Ab-initio calculations on an active site model: hydrogen diformiate with H 2O and H 3O +

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 H 2O and H 3O +. 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 H 2O and H 3O +. Asymmetric hydrogen-bonded structures resulted from these calculations, except for the fully optimized complex with H 2O. In the complexes with H 3O +, 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 H 2O was found to be 20.49 kcal mol −1 and 202.75 kcal mol −1 with H 3O +.