Abstract

LIGAND BASE PHARMACOPHORE MODELING VRTUAL SCREENING AND DOCKING AGAINST TGFRB1 GENE MUTATION IN BREAST CANCER

Kanwal Mushtaq*, Zohaib Bashir, Hanif Khan, Wadeed ul Janan, Syed Faheem Askari and Hussain Ali

Abstract

Introduction: The term “breast cancer” refers to a malignant tumor that has developed from cells in the breast. The types of cells that most commonly give rise to breast cancers are the milk-secreting cells and duct cells, which drain milk from the lobules to the nipple. Factors which add to the burden of breast cancer are the increase in obesity, alcohol consumption, inactivity, and hormone replacement therapy (HRT). Methods: In this research work ligand base pharmacophore modeling have been done against TGFRB1. The compound that are used against breast cancer were downloaded. Compounds were divided into active and experimental sets and pharmachophore model were generated. The shared feature pharmacophore model based on the pharmacophore model was developed. Virtual screening was performed against the shared features pharmacophore model to identify best drug compounds. The identified drug compounds docked with the mutated protein of the gene. Results: The Pharmacohpoere model displayed hydrogen bond donors, hydrogen bond acceptors, aromatic rings, Ionizable positive atoms, In total, 7 compounds were obtained similar to the shared feature pharmacophore model, and docked with the mutated protein. Only one ligand demonstrated best docking results, fulfills all the properties of Lipinski rule of five, non-toxic in nature. In the docked complex the common interactive amino acids identified are His A: 43, Val A: 34, Tyr A: 75, Lys1A:84, which confirmed the validity of a ligand molecule to be used as a drug in the treatment of breast cancer. Conclusion: From Lipinski rule analysis and docking results it is suggested that the ligand can be used as a drug against breast cancer. This research work can be further utilized in laboratory settings to determine its adequacy.

Keywords: Molecular Docking, Pharmacophore, TGFRB1, Toxic, Ligand.