Pharmacoinformatics-based investigation of bioactive compounds of Rasam (South Indian recipe) against human cancer

Abstract

Spice-rich recipes are referred to as “functional foods” because they include a variety of bioactive chemicals that have health-promoting properties, in addition to their nutritional value. Using pharmacoinformatics-based analysis, we explored the relevance of bioactive chemicals found in Rasam (a South Indian cuisine) against oxidative stress-induced human malignancies. The Rasam is composed of twelve main ingredients, each of which contains a variety of bioactive chemicals. Sixty-six bioactive compounds were found from these ingredients, and their structures were downloaded from Pubchem. To find the right target via graph theoretical analysis (mitogen-activated protein kinase 6 (MAPK6)) and decipher their signaling route, a network was built. Sixty-six bioactive compounds were used for in silico molecular docking study against MAPK6 and compared with known MAPK6 inhibitor drug (PD-173955). The top four compounds were chosen for further study based on their docking scores and binding energies. In silico analysis predicted ADMET and physicochemical properties of the selected compounds and were used to assess their drug-likeness. Molecular dynamics (MD) simulation modelling methodology was also used to analyse the effectiveness and safety profile of selected bioactive chemicals based on the docking score, as well as to assess the stability of the MAPK6-ligand complex. Surprisingly, the discovered docking scores against MAPK6 revealed that the selected bioactive chemicals exhibit varying binding ability ranges between − 3.5 and − 10.6 kcal mol−1. MD simulation validated the stability of four chemicals at the MAPK6 binding pockets, including Assafoetidinol A (ASA), Naringin (NAR), Rutin (RUT), and Tomatine (TOM). According to the results obtained, fifty of the sixty-six compounds showed higher binding energy (− 6.1 to − 10.6 kcal mol−1), and four of these compounds may be used as lead compounds to protect cells against oxidative stress-induced human malignancies.

Bioinformatics, Computational Informatics, and Modeling Approaches to the Design of mRNA COVID-19 Vaccine Candidates

“…One of the main functions of the root-mean-square deviation (RMSD) is to depict the average distance between the backbone atoms of the starting structure and the simulated structures when superimposed [111]. As a useful parameter, the RMSD can be utilized to study the equilibration of MD trajectories as well as checking the stability of complex systems during simulation.…”

“…As a useful parameter, the RMSD can be utilized to study the equilibration of MD trajectories as well as checking the stability of complex systems during simulation. This could be achieved by plotting the RMSD of the protein backbone atoms against time to see how the structural shape of the protein changes over time [111]. The RMSD plot was significantly dynamic, with fluctuations occurring after 5 ns.…”

“…The stable conformation was attained at a time range between 75 and 100 nanoseconds, with no significant changes in the results (see Figure 12A). This parameter is useful because it can be used to study how well the behavior of amino acid residues in a target protein changes as it binds to a ligand [111]. Throughout the simulation, the amino acid showed very little fluctuation (Figure 12B).…”

“…To assess changes in surface area, the protein's values were plotted against a function of time. SASA is a significant parameter for determining the extent of receptor exposure to surrounding solvent molecules during simulation [111]. SASA with a higher value indicates more hydrophilicity [113].…”

Aphrodisiac Performance of Bioactive Compounds from Mimosa pudica Linn.: In Silico Molecular Docking and Dynamics Simulation Approach

“…Predicting ligand binding sites from particular sites of a protein structure has numerous implications in protein function elucidation and structure-based drug development [39]. This binding site prediction helps the bioactive molecules to bind and establish sufficient interaction with the target protein, as well as to create a robust ligand-target site interaction to provide the optimal and favorable catalytic effects.…”