In silico study reveals binding potential of rotenone at multiple sites of pulmonary surfactant proteins: A matter of concern

Prem Rajak; Sumedha Roy; Achintya Kumar Pal; Manas Paramanik; Moumita Dutta; Sayanti Podder; Saurabh Sarkar; Abhratanu Ganguly; Moutushi Mandi; Anik Dutta; Kanchana Das; Siddhartha Ghanty; Salma Khatun

doi:10.1016/j.crtox.2021.11.003

In silico study reveals binding potential of rotenone at multiple sites of pulmonary surfactant proteins: A matter of concern

Curr Res Toxicol. 2021 Dec 4:2:411-423. doi: 10.1016/j.crtox.2021.11.003. eCollection 2021.

Authors

Affiliations

¹ Department of Animal Science, Kazi Nazrul University, Asansol, West Bengal, India.
² Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Belgium.
³ Post Graduate Department of Zoology, A. B. N. Seal College, Cooch Behar, West Bengal, India.
⁴ Departments of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
⁵ Post Graduate Department of Zoology, Modern College of Arts, Science and Commerce, Ganeshkhind, Pune, Maharashtra, India.
⁶ Department of Zoology, Gushkara Mahavidyalaya, Gushkara, Purba Bardhaman, West Bengal, India.
⁷ Department of Zoology, The University of Burdwan, Purba Bardhaman, West Bengal, India.
⁸ Post Graduate Department of Zoology, Darjeeling Govt. College, Darjeeling, West Bengal, India.
⁹ Department of Zoology, Krishna Chandra College, Hetampur, West Bengal, India.

Abstract

Rotenone is a broad-spectrum pesticide employed in various agricultural practices all over the world. Human beings are exposed to this chemical through oral, nasal, and dermal routes. Inhalation of rotenone exposes bio-molecular components of lungs to this chemical. Biophysical activity of lungs is precisely regulated by pulmonary surfactant to facilitate gaseous exchange. Surfactant proteins (SPs) are the fundamental components of pulmonary surfactant. SPs like SP-A and SP-D have antimicrobial activities providing a crucial first line of defense against infections in lungs whereas SP-B and SP-C are mainly involved in respiratory cycle and reduction of surface tension at air-water interface. In this study, molecular docking analysis using AutoDock Vina has been conducted to investigate binding potential of rotenone with the four SPs. Results indicate that, rotenone can bind with carbohydrate recognition domain (CRD) of SP-A, N-, and C- terminal peptide of SP-B, SP-C, and CRD of SP-D at multiples sites via several interaction mediators such as H bonds, C-H bonds, alkyl bonds, pi-pi stacked, Van der Waals interaction, and other. Such interactions of rotenone with SPs can disrupt biophysical and anti-microbial functions of SPs in lungs that may invite respiratory ailments and pathogenic infections.

Keywords: ALA, Alanine; ARG, Arginine; ASN, Asparagine; ASP, Aspartic acid; CYS, Cysteine; Carbohydrate recognition domain; GLN, Glutamine; GLU, Glutamic acid; GLY, Glycine; HIS, Histidine; ILE, Isoleucine; LEU, Leucine; LYS, Lysine; Lungs; MET, Methionine; Molecular docking; PHE, Phenylalanine; PRO, Proline; Rotenone; SER, Serine; Surfactant protein; THR, Threonine; TRP, Tryptophan; TYR, Tyrosine; VAL, Valine.