Photinus pyralis luciferase (Ppy luci) : Luciferase enzymes are oxidative enzymes and belong to the class of oxidoreductase enzymes, capable of decarboxylation and ATP hydrolysis. The emission of light is the result of a biochemical reaction in which substrates, i.e. luciferins, are oxidized by luciferase enzyme in presence of ATP, oxygen, and magnesium ions as cofactors.4 The decay of excited oxyluciferin to the ground state generates photons, producing bioluminescent light. Oxyluciferin, CO2, and AMP are generated as byproducts in this reaction. With great advancement in the understanding of protein engineering and synthetic chemistry, attempts have been made to improve bioluminescent activity and specificity. Despite this research establishing significant precedents, factors and interactions contributing to Ppy luci inhibition by resveratrol are not clear. Furthermore, a comprehensive mechanistic framework elucidating how particular physicochemical alterations in structurally analogous inhibitors influence binding, stability, and catalytic interference also remains unattained. In our work, resveratrol and its analogs have been chosen as the model system to understand how subtle changes in the functional group can affect inhibition through a combination of thermodynamic forces, conformational changes, and oxidative interactions. Piceatannol and pterostilbene, analogous to resveratrol, are examined for their inhibitory efficacy on luciferase protein, as they have not yet been extensively investigated.