Figure 1.

The critical subset model. (A) A virion (or virally infected cell) can be viewed as a multivalent receptor containing n identical copies of a given drug target such as HIV-1 protease. Although not physically linked to one another, these copies are spatially constrained within the virus particle or infected cell. (B) Sequential binding of a protease inhibitor (red circle) to the protease dimers (blue crescents) within a virion. The concentrations of the various bound states can be determined by the law of mass action, assuming a single unchanging dissociation constant, K_d. Assuming that successful completion of the relevant step in the virus life cycle requires a critical number c of functional unbound copies of the drug target, f_a can be computed as the concentration of inhibited states divided by the concentration of all possible states (Equation 3). f_u is equal to 1−f_a. Similar arguments can be applied to RT except that the RT molecules are present within the reverse transcription complex in an infected cell.