ABOUT THE MODEL:
This model of HIV Protease shows the molecular surface for each chain of the protein and spheres for the inhibitor, indinavir. The probe radius of the molecular surface was 1.4 angstroms, about that of a water molecule. The scale is 10 million times actual size. This means that the molecule is 5.4 nanometers by 3.9 nanometers by 5.6 nanometers but the physical model swill be 5.4 centimeters by 3.9 centimeters by 5.6 centimeters.
ABOUT THE MOLECULE:
HIV-1 protease (HIV PR) is an aspartic protease that is essential for the life-cycle of HIV, the retrovirus that causes AIDS. HIV PR cleaves newly synthesized polyproteins at the appropriate places to create the mature protein components of an infectious HIV virion. Without effective HIV PR, HIV virions remain uninfectious. Thus, mutation of HIV PR’s active site or inhibition of its activity disrupts HIV’s ability to replicate and infect additional cells, making HIV PR inhibition the subject of much pharmaceutical research.  (http://en.wikipedia.org/wiki/Hiv_protease)
ABOUT THE STRUCTURE (1HSG):
PubMed Abstract: L-735,524 is a potent, orally bioavailable inhibitor of human immunodeficiency virus (HIV) protease currently in a Phase II clinical trial. We report here the three-dimensional structure of L-735,524 complexed to HIV-2 protease at 1.9-A resolution, as well as the structure of the native HIV-2 protease at 2.5-A resolution. The structure of HIV-2 protease is found to be essentially identical to that of HIV-1 protease. In the crystal lattice of the HIV-2 protease complexed with L-735,524, the inhibitor is chelated to the active site of the homodimeric enzyme in one orientation. This feature allows an unambiguous assignment of protein-ligand interactions from the electron density map. Both Fourier and difference Fourier maps reveal clearly the closure of the flap domains of the protease upon L-735,524 binding. Specific interactions between the enzyme and the inhibitor include the hydroxy group of the hydroxyaminopentane amide moiety of L-735,524 ligating to the carboxyl groups of the essential Asp-25 and Asp-25' enzymic residues and the amide oxygens of the inhibitor hydrogen bonding to the backbone amide nitrogen of Ile-50 and Ile-50' via an intervening water molecule. A second bridging water molecule is found between the amide nitrogen N2 of L-735,524 and the carboxyl oxygen of Asp-29'. Although other hydrogen bonds also add to binding, an equally significant contribution to affinity arises from hydrophobic interactions between the protease and the inhibitor throughout the pseudo-symmetric S1/S1', S2/S2', and S3/S3' regions of the enzyme. Except for its pyridine ring, all lipophilic moieties (t-butyl, indanyl, benzyl, and piperidyl) of L-735,524 are rigidly defined in the active site.