Metal-dependent inhibition of HIV-1 integrase by 5CITEP inhibitor: A theoretical QM/MM approach

- The 5CITEP inhibitor has different activity in presence of Mg2+ and Mn2+ ions.
- The QM/MM simulation shown different coordination sphere around divalent cations.
- Particular interactions can be identified in each IN-5CITEP complex by QM/MM approach.
- Theoretical QM/MM simulations elucidated the different activities for 5CITEP inhibitor.

HIV-1 integrase (IN) is a potential target for developing drugs against AIDS. In this letter, QM/MM approach was used to study the inhibition of IN by 5CITEP inhibitor in presence of divalent cations (Mg2+ or Mn2+). In addition, the main interactions occurring in 5CITEP-IN complex and the influence of divalent cations (Mg2+ or Mn2+) in enzymatic inhibition were investigated using B3LYP/6-31+G(d,p)/MM. The results suggest that the Asp64, Asp116 and four crystal water molecules plays a crucial role in cation (Mg2+ or Mn2+) coordination sphere.

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