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

TL;DR

This study explores how pollutants like BPA and AAP affect lung cancer proteins and how anticancer drugs might counteract these effects.

Contribution

The novel contribution is the computational investigation of pollutant-induced protein destabilization and drug mitigation using MD simulations and binding energy calculations.

Findings

AAP causes significant destabilization of Pro-GRP and SOD proteins, while BPA has a milder effect.

Paclitaxel and Sotorasib reduce protein fluctuations and stabilize structures against pollutant effects.

Anticancer drugs modulate pollutant binding at key residues, potentially mitigating destabilization.

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.

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