METHOD FOR PREDICTING ACTIVATION ENERGY USING AN ATOMIC FINGERPRINT DESCRIPTOR OR AN ATOMIC DESCRIPTOR

摘要

The present invention provides a process for constructing an atomic fingerprint descriptor database, and a method for predicting activation energy using an atomic fingerprint descriptor or an atomic descriptor. The method comprises the steps of: (i) calculating an atomic fingerprint descriptor of a substrate; (ii) comparing the calculated atomic fingerprint descriptor with the atomic fingerprint descriptor database constructed by the abovementioned process to select the atomic position at which the metabolic responses by the cytochrome P450 enzyme may occur; and (iii) predicting activation energy for the selected atomic position by using an atomic descriptor. Further, the present invention provides a method for predicting the activation energy of phase I metabolism performed by the CYP450 enzyme through use of an effective atomic descriptor. In detail, the present invention provides a method for predicting the activation energy of the formation of tetrahedral intermediate from a hydrogen separation or aromatic hydroxylation by the cytochrome P450 enzyme through use of an equation containing an effective atomic descriptor. The present invention can rapidly predict activation energy for metabolites of phase I at a practical level even without a docking experiment between any additional CYP450 and the substrate, or a quantum mechanical calculation, to thereby make the development of new drugs using a computer even easier. The present invention may propose a strategy for increasing the bioavailability of drugs through metabolite avoidance design by analysis of the metabolic reaction possibilities of drugs. Further, the activation energy prediction of the present invention enables the prediction of i) metabolic products, ii) the relative speed of metabolism, iii) metabolic regioselectivity iv) metabolic inhibition v) drug interaction, and vi) the toxicity of a metabolite.