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Structural Basis and Distal Effects of Gag Substrate Coevolution in Drug Resistance to HIV-1 Protease

While evolving high levels of resistance to protease inhibitors, HIV-1 accumulates mutations not only in the protease but also its substrates. In this work we revealed the molecular-level interplay between these two types of resistance mutations, and how co-evolution of the substrate restores the structure and dynamics of the complex to allow evolution of resistant viral variants.

Ozen, A.*; Lin, K.-H.*; Kurt Yilmaz, N.*,#; Schiffer, C.A.# “Structural Basis and Distal Effects of Gag Substrate Coevolution in Drug Resistance to HIV-1 Protease”, Proc. Natl. Acad. Sci. USA, Vol. 111, Iss. 45, 15993-15998 (2014). (*joint first author) (#corresponding author).