QSAR, Molecular docking and Molecular dynamics studies simulation of Epigenetic inhibitors

Subject Areas : The Application of Chemistry in Environment

ghasem ghasemi ¹ (Department of Chemistry and Chemical Engineering, Rasht Branch, Islamic Azad University, Rasht, Iran)
babak motahary ² (Depatment of Computer Engineering, Rasht Branch, Islamic Azad university, Rasht, Iran)
Robabe SayadikordAbadi ³ (Department of Chemistry,Rasht Branch,Islamic Azad University, Rasht ,Iran.)
omid alizadeh ⁴ (Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran.)

Received: 2023-02-19 Accepted : 2023-06-09 Published : 2023-05-22

Keywords: Imperialist Competitive Algorithm, Molecular dynamics simulation, Molecular docking, Quantitative structure- activity relationship, Modified chromatin proteins,

Abstract :

Development of QSAR and molecular docking is a key to the elucidation of pathomechanisms of epigenetic diseases. Quantitative structure- activity relationship (QSAR), Molecular docking and molecular dynamics simulation were carried out for some modulators of modified chromatin proteins as anticancer agents. The Imperialist Competitive Algorithm (ICA), partial least squares (PLS), Principle component regression(PCR), Coralsea,and Multiple Linear Regression (MLR) were used to achieve the QSAR models. Suitable descriptors were selected which includes features such as atomic mass, Van der waals volume, shape and geometrical structure of compounds. Then, molecular docking studies were performed using Autodock Vina software which had a high throughput accuracy. Based on features such as number of hydrogen bonds, bonding length, binding affinity, and also root-mean-square deviation (RMSD), the best complex were selected. In general, QSAR, molecular docking and molecular dynamics simulation illustrated that compounds 9 and 14 were selected as suitable agents for the design of anticancer drugs. Drug-likeness descriptors of compounds calculated by DruLiTo. In the molecular docking study, the maximum binding affinity of -9 kcal/mol was obtained between each of enzyme systems (PDB: 3MXF) and the geometric-optimized molecules, representing a strong interaction.