Binding modes of diketo-acid inhibitors of HIV-1 integrase: A comparative molecular dynamics simulation study

► Comparative molecular dynamics simulations on HIV-1 IN bound with L-731,988, L-708,906 and S-1360. ► The acidic end of all the DKA inhibitors studied formed favourable ionic interactions with Lys159. ► The keto-enol parts of these compounds were consistently coordinated to Mg. ► The catalytic residue Glu152 formed a favourable ion-pair interaction with the negatively charged Arg199 on α6 in the most potent DKA inhibitors. ► The complexation with Merck inhibitors and S-1360 significantly constrained the flexible surface loop into an extended or open conformation.