Elucidating the Interaction and Stability of Withanone and Withaferin‐A with Human Serum Albumin, Lysozyme and Hemoglobin Using Computational Biophysical Modeling

Abstract

AbstractWithania somnifera consists of various bioactive compounds, of which withanone (WT−N) and withaferin‐A (WT−A) are known to have many therapeutic properties. To understand drug metabolism and transportation methods, binding of endogenous and exogenous ingredients with transport proteins is of utmost importance. Therefore, to perceive the molecular recognition mechanism of WT−N and WT−A, the association of human serum albumin, human hemoglobin and human lysozyme with WT−N and WT−A were examined, using various in silico techniques. For our study, we have employed both quantum mechanics and molecular mechanics approaches. Resultantly, drug‐like properties and reactivity were calculated with WT−N and WT−A being the most reactive among all the withanolides. The protein HSA in presence of WT−N showed more stability than that of WT−A. However, HL and Hb showed better stability with WT−A as compared to WT−N. Several non‐covalent interactions contributed the utmost part in the binding of WT−N and WT−A with the proteins. The MD simulation studies also showed evidence in the conformational changes and other dynamical properties of the three proteins with both the ligands. Finally, MM‐PBSA results confirmed the free binding energy of the complexes. Our study has provided a substantial recognition of bioactive molecules WT−N and WT−A binding with the carrier proteins, which can significantly affect the pharmacokinetics of these molecules.