Rigidity analysis of HIV-1 protease

Understand

We present a rigidity analysis on a large number of X-ray crystal structures of the enzyme HIV-1 protease using the 'pebble game' algorithm of the software FIRST.

• We find that although the rigidity profile remains similar across a comprehensive set of high resolution structures, the profile changes significantly in the presence of an inhibitor.
• Our study shows that the action of the inhibitors is to restrict the flexibility of the beta-hairpin flaps which allow access to the active site.
• The results are discussed in the context of full molecular dynamics simulations as well as data from NMR experiments.