In silico and docking studies on the binding activities of Keap1 of antioxidant compounds in non-oilseed legumes

Abstract

We used in silico methods to predict the physiochemical and pharmacological characteristics, toxicity, and biological activities of the screened compounds. All compounds showed positive results while calculating their physiochemical and pharmacokinetic descriptors. Using the Prediction of Activity Spectra for Substances (PASS) software on compounds form non-oilseed legumes, we identified compounds (mainly 4 polyphenol compounds) with anti-infective, anti-eczematic, antimutagenic, muco-membranous protector, fibrinolytic, anticarcinogenic, hepato-protectant, cardio-protectant, antioxidant, and astringent effect. PASS predicted HO-1 expression enhancing and free radical scavenging properties for gallic acid, coumaric acid, catechin, and epicatechin. Data about validation protocols for molecular docking of ligand IVV to Keap1 was performed by root mean square deviation (RMSD) value is used to validate docking protocol and representation mainly for analyzing stability of protein and predicting conformational changes of protein. Molecular docking is a powerful technique for studies of receptor-ligand interaction and has led to the discovery of Keap1-Nrf2 small molecule inhibitors. Keap1 inhibits the degradation of Nrf2. Our results suggest that screened compounds from non-oilseed legumes can effectively interact with the Keap1 binding site and dissociate Keap1 and Nrf2. The screened compounds from non-oilseed legumes that displayed high binding affinities with Keap1 are promising new Nrf2 activators. We performed molecular docking to identify the molecular interactions of gallic acid, catechin, and epicatechin with Keap1. Non-oilseed legumes plant is a natural source of potent antioxidant that may prevent diseases and could be potentially used as functional food, nutraceuticals, and drugs.

Keywords

• In silico
• Keap1
• Molecular docking
• Nrf2
• Non-oilseed legumes