In Silico Pharmacokinetic and Molecular Docking Studies of Natural Plants against Essential Protein KRAS for Treatment of Pancreatic Cancer

TL;DR

This study used computational methods to identify plant-derived compounds, especially borneol, as potential inhibitors of KRAS for pancreatic cancer treatment, combining molecular docking, machine learning, and ADME analysis.

Contribution

The paper introduces a novel in silico approach integrating molecular docking and machine learning to identify natural compounds targeting KRAS in pancreatic cancer.

Findings

Borneol showed strong binding affinity to KRAS.

Machine learning predicted borneol's bioactivity as promising.

ADME analysis supported borneol's drug-like properties.

Abstract

A kind of pancreatic cancer called Pancreatic Ductal Adenocarcinoma (PDAC) is anticipated to be one of the main causes of mortality during past years. Evidence from several researches supported the concept that the oncogenic KRAS (Ki-ras2 Kirsten rat sarcoma viral oncogene) mutation is the major cause of pancreatic cancer. KRAS acts as an on-off switch that promotes cell growth. But when the KRAS gene is mutated, it will be in one position, allowing the cell growth uncontrollably. This uncontrollable multiplication of cells causes cancer growth. Therefore, KRAS was selected as the target protein in the study. Fifty plant-derived compounds are selected for the study. To determine whether the examined drugs could bind to the KRAS complex's binding pocket, molecular docking was performed. Computational analyses were used to assess the possible ability of tested substances to pass the Blood Brain Barrier (BBB). To predict the bioactivity of ligands a machine learning model was created. Five machine learning models were created and have chosen the best one among them for analyzing the bioactivity of each ligand. From the fifty plant-derived compounds the compounds with the least binding energies are selected. Then bioactivity of these six compounds is analyzed using Random Forest Regression model. Adsorption, Distribution, Metabolism, Excretion (ADME) properties of compounds are analyzed. The results showed that borneol has powerful effects and acts as a promising agent for the treatment of pancreatic cancer. This suggests that borneol found in plants like mint, ginger, rosemary, etc., is a successful compound for the treatment of pancreatic cancer.