The relationship between biological activity and the electronic structure and transfer of the whole acidic PLA2 molecule in ab initio level.

The electronic structure of the whole molecule of acidic phospholipase A2 (PLA2) from the venom of Agkistrodon halys pallas (A. halys pallas) has been calculated using the extended negative factor counting (ENFC) method in which dimers were calculated at the ab initio level using a minimal basis set, with simulation of the aqueous environment. Hopping conductivities were determined by the use of random walk theory. The results show that the frontier orbitals are mainly localized to residues which are involved in the biological activity of acidic PLA2. The C-terminal region might play some important role in biological activity because of its active electrons. The aromatic patch on the surface of the enzyme, together with two neighbouring acidic residues, has very active electrons that may be responsible for the inhibition of platelet aggregation. Trp30, which is involved in the interfacial recognition region, may transfer its electrons to the aggregated substrate. It is also concluded that the conductivity of the protein is caused mainly by holes transported through the valence band rather than electrons transferred in the conductive band. The a.c. conductivity of acidic PLA2 confirms that proteins, if doped, are amorphous conductors. Moreover, the a.c. conductivities of acidic PLA2 are approximately one order of magnitude higher than those of some other proteins. This suggests that the toxicity of acidic PLA2 may be related to its high a.c. conductivity.