Introduction: In this paper, we have introduced a new atomic descriptor with Klopman index
to determine the local reactive sites of the molecular systems during electrophilic, and nucleophilic
attacks. This index, similar to other local reactivity descriptors but more advanced, has been used as a
realistic descriptor to discover new aspects of molecular structure.
Methods: Nonlinear Least Squares (NLLS) methods to define the parameters maximizing the fit between
the observed points and the computed simulation results were performed according to the Levenberg-
Marquardt (LM) algorithm. We have attempted to demonstrate the structural properties of
compounds that contribute not only basic pharmacophore (b-Pha) but also positive (Auxiliary Group-
AG) or negative (Anti-Pharmacophore Shielding-APS) due to the new local atomic reactivity.
Results and Conclusion: In the 4D-QSAR study, nonparametric regression analysis was used to determine
the adjustable constants. Using the leave One Out Cross-Validation (LOO-CV), antibacterial
activities (pEC50-μM) were predicted as r2
loo-cv (q2) = 0.979, r2
pred (r2) = 0.911, respectively, for 27 training
sets and 9 test set compounds. Also, the rm
(overall) value, which indicates the closeness between the
predicted and corresponding observed data, was calculated to be 0.957. The model obtained by the Molecular
Conformer Electron Topological (MCET) method was compared with the q2
loo-cv and R2
values determined by the CoMFA and CoMSIA methods and more satisfactory results were obtained.