The relationship between biological activity and the electronic structure and transfer of the whole acidic PLA(2) molecule in ab initio level

The electronic structure of the whole molecule of acidic phospholipase A(2) (PLA(2)) from the venom of Agkistrodon halys pallas (A. halys pallas) has been calculated using the extended negative factor counting (ENFC) method i n which dimers were calculated at the ab initio level using a minimal basis set, with simulation of the aqueous environment. Hopping conductivities we re determined by the use of random walk theory. The results show that the f rontier orbitals are mainly localized to residues which are involved in the biological activity of acidic PLA(2). The C-terminal region might play som e important role in biological activity because of its active electrons. Th e aromatic patch on the surface of the enzyme, together with two neighbouri ng acidic residues, has very active electrons that may be responsible for t he inhibition of platelet aggregation. Trp30, which is involved in the inte rfacial recognition region, may transfer its electrons to the aggregated su bstrate. Ht is also concluded that the conductivity of the protein is cause d mainly by holes transported through the valence band rather than electron s transferred in the conductive band. The a.c. conductivity of acidic PLA(2 ) confirms that proteins, if doped, are amorphous conductors. Moreover, the a.c. conductivities of acidic PLA(2) are approximately one order of magnit ude higher than those of some other proteins. This suggests that the toxici ty of acidic PLA(2), may be related to its high a.c. conductivity. (C) 1998 Elsevier Science B.V. All rights reserved.