The present invention provides a method for constructing a
database of atomic
fingerprint descriptors. The invention provides a method for predicting
activation energy using an atomic
fingerprint descriptor and an atomic descriptor, the method comprising the steps of: (i) calculating the atomic
fingerprint descriptor of a substrate; (ii) comparing the calculated atomic fingerprint descriptor with the constructed atomic fingerprint descriptor
database to select an atomic position where
cytochrome P450-mediated
metabolism occurs; and (iii) predicting
activation energy for the selected atomic position using an atomic descriptor. Also, the invention provides a method of predicting the
activation energy of CYP450-mediated phase I
metabolism using effective atomic descriptors. Specifically, the invention provides a method of predicting the activation energy either for
cytochrome P450-mediated
hydrogen abstraction or for tetrahedral intermediate formation in
cytochrome P450-
aromatic hydroxylation using equations including effective atomic descriptors. The method of the invention can rapidly predict activation energy for phase I metabolites at a practical level without having to perform a docking experiment between any additional CYP450 and the substrate, or a
quantum mechanical calculation, thereby making it easier to develop new drugs using a computer. Also, the present invention may propose a strategy for increasing the
bioavailability of drugs through the avoidance of metabolites based on the possibility of
drug metabolism. Furthermore, the method of the present invention proposes new empirical approaches which can also be easily applied to activation energies for various chemical reactions, and makes it possible to explain physical and chemical factors that determine activation energy. In addition, through the prediction of activation energy according to the present invention, it is possible to predict i) metabolic products, ii) the relative rate of metabolism, iii) metabolic
regioselectivity, iv)
metabolic inhibition, v)
drug-
drug interactions, and vi) the
toxicity of a
metabolite.