1. Introduction
HIV protease (HIV PR) is one of the most intensely studied aspartic peptidase, neededfor viral replication implicated in AIDS, during the last 20 years [1]. It was found that water
-
soluble methanofullerene derivative was a competitive inhibitor for this purpose [2, 3].
Therefore, various sizes of fullerene derivatives have been synthesized and their biologicalactivities have been widely measured and reported [4-8]. On the basis of molecular modeling, Friedman et. al.
[2]
anticipated that a C
60
molecule fits nicely into the hydrophobiccavity of the protease specific for HIV-1 because of the steric bulk of C
60
and itscomplementarity to the active site surface of HIV-PR.
The core fullerene moiety wasobserved to bind snugly into the active
site. It was confirmed experimentally that the bindingaffinity of C
60
derivatives is in the low-micromolar to nanomolar range [3]. In addition, themain mechanism of action of these derivatives is hydrophobic interaction.It is known that binding of drug to HIV
-
1 protease alters their physicochemical properties and the potency of binding correlates with the hydrophobicity of the drug.
Therefore, understanding of the structural and the electrostatic features of these compoundswould lead directly to an understanding of the mechanism of their action [9]. As receptor recognized stereo
-
electronic effects, studies of molecular and electronic properties by meansof quantum chemical calculations could also provide essential information in the field of structure based drug design.The present study is an assessment of structural features and electronic propertiestoward an improved understanding of the structure
-
activity relationship of C
60
derivatives toenable a prediction of potent antiviral activity.
The study encompassed 10
compounds asshown in Figure 1.
Optimizations have been made using the Own N
-
layered Integratedmolecular Orbital and molecular Mechanics or ONIOM algorithm [10-12].
The ONIOMscheme allows treating a selected area of a large system at a high level, whereas the rest of the system is treated using a computationally more feasible level of theory. Analyses of electrostatic potentials (ESP) and molecular properties have been investigated in detail.
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