Nucleocapsid protein reactivity

Maynard, A. T., Huang, M., Rice, W. G., and Covell, D. G. 1998. Reactivity of the HIV-1 nucleocapsid protein p7 zinc finger domains from the perspective of density-functional theory. Proc. Natl. Acad. Sci. USA 95 11578-11583. 

From the theoretical point of view, the electrophilicity concept has been recently discussed in terms of global reactivity indexes defined for the ground states of atoms and molecules by Roy et al.18 19. In the context of the conceptual density functional theory (DFT), a global electrophilicity index defined in terms of the electronic chemical potential and the global hardness was proposed by Maynard et al.20 in their study of reactivity of the HIV-1 nucleocapsid protein p7 zinc finger domains. Recently, Parr, Szentp ly and Liu proposed a formal derivation of the electrophilicity, co, from a second-order energy expression developed in terms of the variation in the number of electrons.21... 

This measures the propensity of electrophilic attack and is used [74] in understanding the reactivity of the human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein p7 (NCp7) when reacted with a variety of electrophilic agents. 

Retroviral nucleocapsid proteins have been proposed as an attractive target for HIV inactivation and therapy [9-11] due to the presence of a highly conserved motif (zinc fingers) that is required for their activity. Chemical reactivity towards these sequences has been demonstrated with compounds bearing different active groups, which constitute a virtual library numbering in the tens of thousands. 

The data listed in Table I and depicted in Figure 5 were obtained using a B3P86 frinctional. The calculated values of redox potential in aqueous solvent for a ven compound were subsequently compared with its reactivity (NC values) towards mV-1 nucleocapsid protein (see below). 

Our investigation of the redox properties of electrophilic compounds shows that their rate of reaction with HIV-1 nucleocapsid protein increases in a linear manner with oxidative power. Moreover, a threshold exists below which no reaction with HTV-l NCp7 can be detected in our standard assay. Since DFT analysis of these electrophilic reagents yields a ranking of redox propensities, we propose that the redox properties of compounds untested experimentally can be predicted ab initio. Conversely, knowledge of the oxidation potential of a compound (which has been determined for a large number of chemical species) would permit an initial prediction of its reactivity against nucleocapsid proteins. For instance, if the redox potential of an untested compound was below that of compounds known to be below the reactivity threshold uncovered in our study, they would be predicted to be unreactive and pre-screened out of a test series. 

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