Virtual Screening through Molecular Docking Analysis to Identify Potential Natural Inhibitor(s) of Lyn Tyrosine Kinase- An In-silico Approach

Chandreyi Ghosh,Moumita Saha,Sirshendu Chatterjee,Soham Banerjee,Sohini Kulavi,Titav Sengupta

doi:10.9734/jpri/2021/v33i50a33385

Abstract

Breast cancer on becoming one of the leading cancer types, emerged as an important barrier in increasing life expectancy of the overall population. In the current study, some compounds were screened based on literature survey for the identification of natural bioactive compounds as potential inhibitors of Lyn tyrosine kinase. Therefore, a multi-step molecular docking was carried out using AutoDock embedded in the MGL Tools. After initial screening, molecules having a higher docking score and binding free energy compared to Tamoxifen were considered for further assessment. Some already known synthetic lyn tyrosine kinase inhibitor have been used for better understanding of the comparative study. Based on in silico Lipinski filter analysis, toxicity prediction, pharmacokinetic analysis, four compounds were proposed to be promising inhibitors of Lyn tyrosine kinase. Furthermore, the binding interactions of all proposed inhibitors of Lyn showed strong ligand efficiency in terms of energy score obtained with the help of molecular modelling analyses. Hence, the proposed compounds out of which three are bioactive compounds might be taken forward as potential next-generation Lyn kinase inhibitors for managing Lyn associated breast cancer after experimental authentication.

Highlights

Cancer is a special kind of heterogeneous disease which is mainly triggered by the irreversible impairments of cellular homeostasis and their functions
On analysing the RMSF plots derived for each complex of Lyn with proposed inhibitors and Bosutinib, very interestingly we found that the fluctuation pattern of the flavonoids were almost same to the Bosutinib (Lyn inhibitor)
A detailed molecular docking based virtual screening was done to identify the potential natural inhibitors for Lyn tyrosine kinase (PDB ID: 3A4O). This is to pave a path for dysregulated Lyn associated breast cancer therapeutic applications

Summary

Introduction

Cancer is a special kind of heterogeneous disease which is mainly triggered by the irreversible impairments of cellular homeostasis and their functions. Breast cancer, being one of the common cancer types, women of every age are being detected with this deadly disease [3]. Lyn is one of the most important members of src family kinases (tyrosine), it has several regulatory impacts upon the signalling intermediates. It is crucial for modulating and relying several to different input in order to control various outputs, like proliferation, differentiation, apoptosis, migration and metabolism . Within same and as well as different cellular contexts Lyn can regulate and maintain both the negative and positive processes of signalling [5]. LYN has been identified as a mediator of invasion and a potential therapeutic target, with certain significance in clinically-aggressive basal-like breast cancer [6]

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Conclusion