Hydrogen-bonding interactions in the binding of loop 1 of fasciculin 2 to Torpedo californica acetylcholinesterase: a density functional theory study

In the present study, the interactions of model complexes at the interface between loop1 of fasciculin 2 (Fas2) and acetylcholinesterase (AChE) are theoretically explored. Three interaction models based upon the crystal structure of the complex of Fas2 with AChE from Torpedo californica (PDB code ) were fully optimized at the B3LYP/6-311G(d,p) level of theory. The atoms-in-molecules (AIM) approach was employed to characterize the corresponding noncovalent hydrogen bonds through the densities and the Laplacians of electron densities at the bond critical points. The total interaction energy of loop 1 (Fas2) with AChE is predicted to be -99.4 kcal/mol. It is concluded that the Fas2 residue Thr8, which contributes more than half of the total binding energy, plays the most important role among the three binding sites. The energy decomposition results through the Kitaura-Morokuma scheme suggest that the electrostatic term is the major component of the entire interaction energy. The positive cooperativity effect revealed in the Thr8(F)-related models was confirmed through the geometry characteristics, AIM results, and the energy decomposition analysis.