Molecular Disruption of Pulmonary Surfactant Proteins by Airborne Pollutants: An Integrative In-Silico Toxicology Approach

Pulmonary surfactant proteins (SP-A, SP-B, SP-C, and SP-D) are essential regulators of alveolar surface tension and pulmonary immune defense, constituting a critical frontline barrier against airborne xenobiotics. Increasing environmental pollution exposes the respiratory system to diverse toxicants capable of impairing surfactant functionality and promoting pulmonary pathology. This study aimed to evaluate the molecular interactions between environmentally prevalent airborne pollutants and human surfactant proteins using an integrative in-silico toxicology framework.
A multi-tiered computational strategy was employed to assess interactions between 87 airborne pollutants and surfactant proteins. Structure-based molecular docking using AutoDock Vina identified high-affinity ligand–protein interactions, while molecular dynamics simulations evaluated complex stability and conformational changes. Binding free energy calculations and interaction profiling further characterized pollutant-induced structural perturbations within surfactant proteins.
Results revealed that several pollutants, particularly benzo[a]pyrene and crotonic acid, exhibited strong binding affinities with surfactant proteins, suggesting potential disruption of structural integrity and functional domains. Molecular dynamics analyses demonstrated notable conformational fluctuations and altered hydrogen-bonding networks, indicating compromised protein stability and possible impairment of surfactant activity. Interaction mapping highlighted key residues involved in pollutant binding, providing mechanistic insights into toxicity pathways.
These findings suggest that airborne pollutants may directly interfere with pulmonary surfactant proteins at the molecular level, potentially contributing to respiratory dysfunction, inflammatory responses, and increased susceptibility to lung disease. The study underscores the importance of integrating computational toxicology approaches for early prediction of pollutant-induced respiratory toxicity and risk assessment.
Overall, this research provides novel mechanistic insights into pollutant-surfactant interactions and offers a valuable platform for identifying environmental hazards affecting respiratory health, supporting the development of preventive strategies and regulatory policies.

Dr. Saba Beigh is an Associate Professor of Toxicology and Pharmacology at Al-Baha University, Saudi Arabia. She obtained her Ph.D. in Toxicology and Pharmacology from Jamia Hamdard University, India, and completed her postdoctoral training in Nanotoxicology at the University of Strasbourg, France. Her research focuses on pulmonary toxicology, nanotoxicology, oxidative stress, immunopharmacology, and computational pharmacology. She has authored numerous publications in peer-reviewed journals and has been honored with awards including the EUROTOX Best Poster Award and the CSIR-SRF Fellowship.