The continuous chain of residues (Thr7 to Ala12) of Loop1 of Fas2 (F1) and its interaction
with the peripheral binding sites (Tyr70-Val71) of AChE (P1) has been studied. Our
results suggest that the flexibility of Loop1 might be caused by either the partially protonated
guanidine group of Arg11 under experimental conditions or by the interaction with the
negatively charged center of substrates. The binding energy of F1-P1 is predicted to be -16.6
kcal/mol at the B3LYP/6-311G(d,p) level, which is assumed to originate from one isolated
O7¡HN10 H-bond, one possible O10¡HC71 unconventional O¡HC type H-bonding, and
the improved ¦Ð-bonding cooperativity around the peptide group of the AChE segment Tyr70-
Val71. The classical Kitaura-Morokuma energy decomposition analysis, the NPA charge
analysis, and the AIM analysis consistently reveal that the peptide group in segment P1 is
more polarizable, which might play the key role in the interactions between F1 and P1. The
PCM solvent effect corrected results reveal decrease of the interaction energy of the considered
model. The importance of Thr8 of Fas2 in the P-site binding of AChE is also concluded.
Site-directed mutations on either the Fas2 residue of Thr8 or the AChE residue of Tyr70 are
expected to alter the binding behavior of the Loop1 of Fas2 with AChE.