Comprehending the intermolecular interaction of JAK inhibitor fedratinib with bovine serum albumin (BSA)/human alpha-1-acid glycoprotein (HAG): Multispectral methodologies and molecular simulation

Abstract

The primary coverage of this paper is to investigate the molecular interaction of JAK2 inhibitor, fedratinib (FED) with BSA/HAG proteins through multispectral approaches and molecular docking as well as MD calculation. Arrival at a conclusion, the endogenous fluorescence of BSA/HAG protein was quenched separately in the form of static and mixed quenching. The FED-BSA and FED-HAG complexes with the stoichiometric ratio of 1:1 were formed in the interaction process. And, The Kb values of these complexes were of 104–105 M−1 and 105–106 M−1, respectively, representing that the FED-HAG complex exhibited a comparatively high affinity compared to the FED-BSA complex. It is confimed that FED inserted into the interface area between subdomain IIA and IIB of BSA (marked as site II') and the bucket-shaped hydrophobic cavity of HAG, respectively, resulting in the slight alteration in the secondary structure of BSA/HAG and the micro-environment round Tyr and Trp residues. The expetimental results also confirmed that van der Waals forces (VDW), hydrogen bonds and hydrophobic interaction played a dominant role in the formation of two stable complexes. The above experimental results were supplemented and verified through molecular docking and MD simulation. Meanwhile, the effects of common ions on affinity were explored. This study could shine a light on evaluating the pharmacological properties of the JAK inhibitor FED, understanding the distribution and operation of the drug in the body, and leading to the development of the creation of novel medication devise.