Identification of potential phytochemical inhibitors for the proven six chronic obstructive pulmonary disease biomarkers – A molecular dynamics study

COPD is a multifactorial lung disease causing breathing difficulties in individuals and is becoming a major health concern worldwide. The unclear pathogenic mechanism and high mortality rate urge the development of drugs against this disease. In this study, around six COPD biomarkers identified from the preceding research through integrated gene expression analysis were taken as COPD target proteins. A total of 3307 phytocompounds were included in the COPD phytocompound library from 59 therapeutic plant sources. Furthermore, a crucial three-step virtual screening process (Absorption, Distribution, Metabolism, and Excretion, respiratory nontoxicity, less harmful and nontoxic compound category) was implemented to filter the potential drug-like phytocompounds. As a result, 160 phytocompounds were filtered with desired Absorption, Distribution, Metabolism, Excretion and Toxicity properties. The filtered 160 phytocompounds were docked against six COPD target proteins and the best-docked complexes were identified through visual inspection based on six unique parameters in SeeSAR. Furthermore, the best docked complexes were subjected to molecular dynamics simulation studies to assess the stability and conformational changes of the complexes. The presence of few amino acid residues within the crucial active, allosteric and catalytic sites of the six target proteins were revealed from the binding interaction types and major residual fluctuations from molecular docking and dynamic simulation studies respectively. This is indicative of the potential inhibitory activity of phytocompounds against the COPD biomarkers. Here we report the identified phytocompounds as a promising lead molecule for the six COPD biomarkers through <i>in silico</i> analysis opening new avenues in COPD pathogenesis and treatments. Communicated by Ramaswamy H. Sarma