Structural modeling for DNA binding to antioxidants resveratrol, genistein and curcumin

•Intercalative and groove binding modes were explored for polyphenol-DNA adducts.•Resveratrol and genistein form both intercalation and groove binding adducts.•Intercalation leads to more stable complexes than groove binding.•Curcumin adduct formation is only via groove binding.•Resveratrol forms more stable complexes than genistein and curcumin.

Several models are presented here for the bindings of the antioxidant polyphenols resveratrol, genistein and curcumin with DNA in aqueous solution at physiological conditions. Multiple spectroscopic methods and molecular modeling were used to locate the binding sites of these polyphenols with DNA duplex. Structural models showed that intercalation is more stable for resveratrol and genistein than groove bindings, while curcumin interaction is via DNA grooves. Docking showed more stable complexes formed with resveratrol and genistein than curcumin with the free binding energies of −4.62 for resveratrol-DNA (intercalation), −4.28 for resveratrol-DNA (groove binding), −4.54 for genistein-DNA (intercalation), −4.38 for genistein-DNA (groove binding) and −3.84 kcal/mol for curcumin-DNA (groove binding). The free binding energies show polyphenol-DNA complexation is spontaneous at room temperature. At high polyphenol concentration a major DNA aggregation occurred, while biopolymer remained in B-family structure.

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