Deciphering the Binding Mechanism of Noscapine with Lysozyme: Biophysical and Chemoinformatic Approaches

Abstract

Lysozyme is a well-characterized protein in terms of its structure, dynamics, and functions. It has thus emerged as a potential target to understand protein–drug interactions. The aim of our study is to gain a biophysical outlook on the interaction of lysozyme (Lyz), a well-known model protein, with Noscapine, a potent tubulin-binding anticancer drug. Noscapine (Nos) is effective against a wide range of cancer and shows low toxicity and few side effects. We report the underlying mechanism of complex formation between Nos and Lyz using spectroscopic and advanced computational avenues. The spectroscopic techniques, that is, absorption and steady-state and time-resolved fluorescence, proved that Lyz–Nos forms a complex, and the quenching mechanism was of the static type. The binding constant was in the order of 103 indicative of moderate binding, while the stoichiometry of the protein–drug complex was 1:1 at 298 K. The secondary structural analysis using CD and UV thermal denaturation further confirmed the conformational changes in the protein upon binding with Nos. Molecular dynamics simulation studies confirmed the stable binding with minimum deviations in RMSD. The above conclusions are significant to the development of the pharmacokinetics and pharmacodynamic properties of Nos, and its successful interaction with a versatile protein like Lyz will help in overcoming its previous limitations.

Noscapine as Anticancer Agent & Its Role in Ovarian Cancer

“…The results demonstrated synergistic effect of Noscapine and Cisplatin together with reduced tumor volume by 78% as compared with 38% by Cisplatin or 35% by Noscapine alone in murine xenograft lung cancer model [22]. The mechanistic interaction of Noscapine and Lysozyme has been recently studied by Damini [23]. The study investigated their conformational changes and helped in understanding biophysical properties on interaction of Lysozyme with Noscapine.…”

Molecular Binding Mechanism and Pharmacology Comparative Analysis of Noscapine for Repurposing against SARS-CoV-2 Protease

“…Molecular docking assays have been widely applied to study and understand the mechanistic interaction of drugs with target protein receptors. − Molecular dynamics simulation analyses help with the elucidation of stable binding of drugs with the target protein. It tells about the atomic fluctuations of the interaction complex system by RMSD, RMSF, and other parameters. − Also, computational algorithms have been widely engaged to determine the physicochemical properties of drugs and other therapeutic targets . Herein, MD simulation framework provided the considerable molecular binding mechanism of noscapine and high repurposing potency against COVID-19.…”

“…It tells about the atomic fluctuations of the interaction complex system by RMSD, RMSF, and other parameters. 24−26 Also, computational algorithms have been widely engaged to determine the physicochemical properties of drugs 27 and other therapeutic targets. 28 Herein, MD simulation framework provided the considerable molecular binding mechanism of noscapine and high repurposing potency against COVID-19.…”

Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19)

“…17,18 Computational techniques are essential in these early stages of research as they can provide useful data in a short period, boosting the subsequent phases of research. [19][20][21][22][23][24][25] For instance, the accurate prediction of the binding affinity represents one of the most interesting eld of investigation. [26][27][28] Moreover, to date there is no vaccine available, and the computational repurposing campaigns are privileged approaches as they deal with already approved drugs that will not need to pass the entire pre-clinical phase.…”