Probing the acetylcholinesterase inhibition of sarin: a comparative interaction study of the inhibitor and acetylcholine with a model enzyme cavity

Interaction energies have been estimated between sarin and a model enzyme cavity of acetylcholinesterase (ACHE) using the density functional and M?ller-Plesset second-order perturbation (MP2) levels of theories. The calculated interaction energies have been compared with those of acetylcholine and the same model ACHE cavity. The ACHE...sarin and ACHE...acetylcholine (Ach) structures have been optimized using DFT based two-layer ONIOM hybrid calculations. The nature of interactions has been investigated in detail using an interaction energy partitioning technique. The effects of solvation on the interaction energies have also been taken into account. An inhibition mechanism during the uptake of sarin inside the ACHE cavity has been proposed from the comparison of the energetics of the ACHE...sarin and ACHE...Ach complexes.