Interaction of β-Lactoglobulin with Resveratrol: Molecular Docking and Molecular Dynamics Simulation Studies

Resveratrol (3,5,4′-trihydroxystilbene) (Fig. 1) was first isolated in 1940 as an ingredient of the roots of white hellebore (Veratrum grandiflorum O. Loes) and has since been found in about 70 plant species, including grapes, mulberries and peanuts.1 It can also be found in food products and beverages such as peanut butter, red wine and grape juice.2,3 It provides cardioprotection in red wine through multiple routes like antioxidant action,4 activating NO production,5 inhibiting low-density lipoprotein,6 hindering platelet aggregation,7 and promoting anti-inflammatory effects.4 Resveratrol protects the heart at a relatively low concentration (about 2.5 to 10 mg kg–1 doses).8 In contrast, resveratrol destroys cancer cells at relatively higher doses.8–11 For example, it causes death of cancer cells by apoptosis at 100–1000 mg kg–1 doses. Resveratrol exists as transand cis-isomers. Most of its biological activities are attributed to the trans-isomer. Although a few biological activities of cis-resveratrol have been reported, which include the inhibition of collagen-induced platelet aggregation and kinase activity related to cancer,7,12 it is unclear whether cis-resveratrol might extensively exhibit biological activities comparable to those of the trans-isomer. In solution, trans-resveratrol converts to its cis-isomers under the exposure to light.13,14 The stability of trans-resveratrol, which ranges from hours to several days, depends on the pH of the solution.13 It may form complexes with natural and modified cyclodextrins, increasing both its stability and water solubility.14 Due to the low water solubility of resveratrol, it must be bound to protein or conjugated to remain at a high concentration in serum.15 Bovine β-lactoglobulin (BLG) has been one of the most extensively studied proteins in the history of protein science.16–19 The major reason for this is simply its abundance in cow’s milk; the concentraInteraction of β-Lactoglobulin with Resveratrol: Molecular Docking and Molecular Dynamics Simulation Studies