Computational Prediction of Antibody Binding Sites on Tetracycline Antibiotics: Electrostatic Potentials and Average Local Ionization Energies on Molecular Surfaces

Abstract

Enzyme linked immunosorbent assay (ELISA) was used for the analysis of tetracycline, chlortetracycline, oxytetracycline, and their transformed compounds in environmental water samples. The antibodies employed in ELISA showed high relative affinity for tetracycline, epitetracycline, chlortetracycline, and epichlortetracycline as compared to anhydrotetracycline, epianhydrotetracycline, and anhydrochlortetracycline. The specificity and crossreactivity of these antibodies are discussed in relation to the electrostatic potentials and average local ionization energies computed on the molecular surfaces of tetracycline antibiotics and their transformed compounds with an objective of identifying common features as well as differences that may be related to the experimentally observed variation in cross-reactivity values. The computations were performed at both the HF/STO-3G and HF/6-31+G* levels using the Gaussian 98 program. The results in this study are based upon molecular electrostatic potentials and local ionization energies computed on isodensity molecular surfaces. The surface electrostatic potentials are characterized in terms of a group of statistically defined quantities, which include the average deviation, the positive, negative, and total variances, positive and negative surface extrema, and a parameter indicating the degree of electrostatic balance.

Structural analysis of neutral tetracycline using anharmonicity of delocalized vibrations

“…The results are helpful for an effective start in computational modelling of tetracycline docking to enzymatic sites. 23 The approach we demonstrate here is of general value for structural analysis of molecular systems of complex nature.…”

“…The task is of an obvious necessity in effective computational modelling of tetracycline docking to enzymatic sites. 23,36 Fig. 6 FTIR and 2DIR spectra of tetracyclines in DMSO (a).…”

DFT/TDDFT investigation of the stepwise deprotonation in tetracycline: pKa assignment and UV–vis spectroscopy

“…Several theoretical investigations on tetracyclines have been reported, using ab initio [29][30][31][32] and DFT [33][34][35][36][37][38][39][40] calculations, dealing with their possible conformations [35][36][37], their complexation with different metals [33,39,40], and their vibrational and NMR spectroscopy [34,35]. Regarding the electronic spectra, the simulation of the absorption spectra has been performed for the neutral tetracycline [2] and for the related anhydrotetracycline by semiempirical calculations [41].…”