Figure 2.  Movements of the NNRTI binding pocket that accompany NNRTI binding.  In the available RT structures, there is no NNRTI binding pocket if there is not a bound NNRTI.  In the absence of a bound NNRTI (shown as a yellow backbone with green amino acid side chains), F227, Y181, Y188, and W229 come together to form a compact hydrophobic core.  Binding of an NNRTI (the NNRTI has been removed to make the comparison of the positions of the amino acid side chains easier to see) is accompanied by movements of the backbone (shown in blue) and the amino acid side chains.  This creates the space occupied by the NNRTI.  The beta12-beta13 loop lifts, moving W229 and F227 with it.  Y181 and Y188 pivot (leftward in the drawing), creating more space.  In practice, the exact positions of the individual amino acid side chains differ depending on the nature of the bound NNRTI.  The positions of the side chains adjust so that the shape of the hydrophobic pocket matches the shape of the bound drug.