Identification of Phytomolecules as Isoform and Mutation specific PI3K-α inhibitor for protection against Breast Cancer using e-Pharmacophore modeling and Molecular dynamics simulations

Abstract

Mutations in PI3K-α contribute to a substantial proportion of breast cancer cases, particularly in HR+/HER2- subtypes. Inhibition of mutated PI3K-α will result in decrease in the progression of tumor growth. Nature has been a source of drug for numerous with compounds like Vincristine or Trabectedin, being use in cancer therapy. Therefore by using computational techniques like e-pharmacophore and molecular dynamics simulation, was used to identify natural compounds as an inhibitor of mutant and isoform specific PI3K-α. e-Pharmacophore was generated using Inavolisib drug (PDB:8EXV) and phase screening was done using Molport database for Natural compounds. After ligand docking, induced-fit docking, and ADMET analysis, Seven compounds were shortlisted for molecular dynamics simulation analysis. Out of those seven compounds, only three compounds, namely STOCK1N-85097, STOCK1N-85998, and STOCK1N-86060, show good RMSD, RMSF, Rg, SASA, PCA, FEL, and Total energy.