Interaction of Indole Derivative with Human Serum Albumin: A Combined Spectroscopic and Molecular Dynamics Study

In the present work, we have studied the interaction of synthesized indole derivative (ID) with a model protein, human serum albumin (HSA). Various spectroscopic and molecular dynamic simulation methods were employed to characterize the binding between ID and HSA. ID showed strong binding affinity towards HSA (1.86x106 M−1) and quenched the fluorescence intensity of HSA by dynamic quenching mechanism. The existence of dynamic quenching mechanism in ID‐HSA interaction was further confirmed by lifetime measurement study. ID‐HSA interaction was favored by hydrophobic forces. The binding site for ID on HSA was examined by site probe competitive experiments and molecular docking studies. The results revealed that ID was bound to HSA primarily at site I of subdomain IIA. Absorption, 3D fluorescence and circular dichroism (CD) studies provided information on the conformational and microenvironmental changes in HSA upon binding to ID. Various spectroscopic and molecular docking tools were employed to understand the ID‐HSA binding profile such as mechanism of interaction, binding affinity of ID towards HSA, number of binding sites, nature of binding force, specific binding site for ID in HSA and extent of energy transfer from HSA to ID. Further, alterations in the structure of HSA upon complexation with ID were discussed.