Computational analysis of the aminic subsite of PGA explains the influence of amine structure on enantioselectivity

PGA in toluene catalyses the resolution of aromatic amino acids with high enantiomeric excess (>90%) whereas for aliphatic amino acids the enantiomeric excess is far lower (<20%). Molecular modelling explains such a behaviour in terms of interactions in the active site and energies of the intermediate tetrahedral complexes. In this paper, the GRID program has found an innovative application in biocatalysis. The GRID analysis indicates that two different regions can be distinguished within the aminic subsite of PGA active site, the first being mainly hydrophobic and the second one hydrophilic. As a consequence, aromatic l-enantiomers are highly energetically favoured with respect to the d-enantiomers. The low difference in energy between the two enantiomers of aliphatic amino acids explains the poor enantioselectivity of PGA for this kind of compounds.