Molecular modeling, simulation and principal component analysis of binding of resveratrol and its analogues with DNA.

Structure-based drug designing has become a significant subject of research, and several clinically promising DNA binding compounds were evolved using this technique. The interaction of an octamer DNA sequence d(CCAATTGG) with a natural stilbene, resveratrol and its analogues have been studied using molecular docking method. Out of the ten compounds studied, seven compounds were found to bind to the minor groove of AATT segment of the sequence. Pterostilbene, a natural analogue of resveratrol, showed the lowest binding energy. Rhaponticin, a natural analogue of resveratrol and digalloylresveratrol, a synthetic ester of resveratrol bind to the major groove of the AATT segment while dihydroresveratrol binds to the minor groove of GC terminal base pair. ADMET (Absorption, distribution, metabolism, excretion and toxicity) study showed that all compounds obey Lipinski rule and are accepted as orally active drugs based on different physicochemical descriptors. Molecular dynamics simulations were performed for the complex with lowest binding energy and trajectory analysis were performed. Principal component analysis has been performed to underline the prominent motions in alone DNA and when it is bound to pterostilbene. AbbreviationsADMETAbsorption, distribution, metabolism, excretion and toxicityDIGDigalloyl resveratrolDNADeoxyribonucleic acidELElectrostatic energyENPOLARNonpolar solvation energyESURFSurface areaGBGeneralized BornHBAHydrogen bond acceptorsHBDHydrogen bond donorsLGALamarckian genetic algorithmMDMolecular dynamicsPBPoisson-BoltzmannPCAPrincipal component analysisPTPterostilbeneRMSDRoot mean square deviationSASimulated annealingTLX3T-cell leukemia homeobox 3VDWvan der WaalsCommunicated by Ramaswamy H. Sarma.