Evidence of a butterfly-like configuration of structurally diverse allosteric inhibitors of the HIV-1 reverse transcriptase.

Although many physicochemical properties of chemically diverse nonnucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) differ, there is a common three-dimensional feature. This shape is a rigid butterfly-like configuration which fits well into a sizable internal cavity of the allosteric area of the enzyme. The number of amino acids of the allosteric receptor sites that contribute to NNRTIs binding correlates with the degree of the butterfly-like shape. It seems that molecular rigidity of the butterfly-like shape, the drug affinity and the probability of resistance development are closely related.