Electronic Properties for Medicine Inhibiting Cancer Metastasis (2) : Molecular Mechanics and Molecular Orbital Calculations for Urokinase

Abstract

As an efficient medicine for inhibiting cancer metastasis without a side effect, a chimeric protein including urokinase was developed. For the amino terminal fragment (ATF) of the urokinase, which is a receptor-binding site of this chimeric protein, we investigated its stable structures by the AMBER force field. Their electronic properties were also investigated by semiempirical molecular orbital (MO) method. From the obtained energy levels and distributions of HOMO (highest occupied MO) and LUMO (lowest unoccupied MO), we found that the 30th Trp and the Cys-Cys bridge of the 13th-31st amino acids of ATF are related with the chemical reactivity of ATF. Furthermore, the effect of amino-acid mutations on the chemical reactivity of ATF was evaluated by the semiempirical MO method.