Environmental Pollutants and Protein Destabilization in Lung Cancer: Anticancer Drug Strategies for Structural Stability Publisher



Rasoolzadeh R ; Faraji H ; Baptista L ; Vajedi FS ; Nikoofard V ; Costa LT ; Carneiro JWDM
Source: ACS Omega Published:2026

Abstract

Environmental pollutants such as bisphenol A (BPA) and aminoantipyrine (AAP) are increasingly recognized for their detrimental effects on human health, particularly in lung cancer progression. These pollutants can alter protein conformations and interfere with anticancer drug efficacy. Among key lung cancer biomarkers, pro-gastrin-releasing peptide (Pro-GRP) and superoxide dismutase (SOD) play crucial roles in tumor progression and oxidative stress regulation, respectively. However, the molecular mechanisms underlying pollutant-induced disruptions in these proteins remain poorly understood. In this study, we employed molecular dynamics (MD) simulations, molecular docking, and binding free energy calculations to investigate the effects of BPA and AAP on the structural dynamics of Pro-GRP and SOD. Additionally, we assessed the impact of two anticancer drugs, Paclitaxel and Sotorasib, in mitigating pollutant-induced conformational instability. Our results suggest that AAP induces significant destabilization in both proteins, while BPA exhibits a milder effect. RMSD and RMSF analyses reveal that both Paclitaxel and Sotorasib stabilize protein structures by reducing fluctuations and preserving their native conformations. MM/PBSA analysis further indicates that anticancer agents modulate pollutant binding at critical residues, potentially mitigating their destabilizing effects. These findings provide computational evidence of pollutant–drug–protein interplay and suggest that environmental exposures could influence drug–protein interactions in lung cancer. As this work is computational and hypothesis-generating, experimental validation will be essential to establish biological and clinical relevance. © 2026 The Authors. Published by American Chemical Society