System-level protein interaction network analysis and molecular dynamics study reveal interaction of ferulic acid withPTGS2as a natural radioprotector

AbstractAbstractFerulic acid is a crucial bioactive component of broccoli, wheat, and rice bran and is also an essential natural product that has undergone significant research. Ferulic acid's precise mode of action and effect on system-level protein networks have not been thoroughly investigated. An interactome was built using the STRING database and Cytoscape tools, utilizing 788 key proteins collected from PubMed literature to identify the ferulic acid-governed regulatory action on protein interaction network (PIN). The scale-free biological network of ferulic acid-rewired PIN is highly interconnected. We discovered 15 sub-modules using the MCODE tool for sub-modulization analysis and 153 enriched signaling pathways. Further, functional enrichment of top bottleneck proteins revealed the FoxO signaling pathway involved in enhancing cellular defense against oxidative stress. The selection of the critical regulatory proteins of the ferulic acid-rewired PIN was completed by performing analyses of topological characteristics such as GO term/pathways analysis, degree, bottleneck, molecular docking, and dynamics investigations. The current research derives a precise molecular mechanism for ferulic acid's action on the body. This in-depth in silico model would aid in understanding how ferulic acid origins its antioxidant and scavenging properties in the human body.Communicated by Ramaswamy H. SarmaKeywords: ferulic acidantioxidantdockingMD simulationsGO term AcknowledgementsThe authors thank, Nitte (Deemed to be University), Mangalore, India for providing all the facilities to complete this work.Disclosure statementNo potential conflict of interest was reported by the authors.Author's contributionsTG & GP designed and carried out the experiments; contributed to the interpretation of the results, conceptualization the work and wrote the main manuscript text. AK assisted in carrying MD simulations.Data availability statementAll the data we generated in this paper is available in the body of the manuscript as supporting figures and tables. We do not have any ethical or legal consideration for not to make our data publicly available.Additional informationFundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.