Docking of raltegravir to HIV-1 integrase structure ensemble

Docking of the drug raltegravir to HIV-1 integrase (IN) was performed based on the established Relaxed Complex Scheme (RCS) method which accounts for the flexibility of both receptor and ligand in molecular docking. Two representative butterfly-like structures of raltegravir were identified and both of them mimicked the binding mode of 5CITEP with similar ligand-receptor interactions. Furthermore, the results that raltegravir interacted with magnesium by intermediate water molecules indicate the importance of water molecules at the binding site which has always been ignored in the docking studies of IN inhibitors. Taking these water molecules into consideration gives more insight into the design and development of the second generation IN inhibitors.