Molecular bioprospection of Helianthus annuus L. (sunflower) cypselae for antidiabetic therapeutics through network pharmacology, density functional theory and molecular dynamics simulation

Waste to Medicine: Evidence from Computational Studies on the Modulatory Role of Corn Silk on the Therapeutic Targets Implicated in Type 2 Diabetes Mellitus

“…Except for 4-hydroxycinnamic acid, the lesser average RMSF values observed in all the investigated phytocompounds against HCAR2 compared to the standard HCAR2 complexes indicated less flexible movements. This observation suggests the lesser flexibility of HCAR2 amino acid residues, following the binding of the topranked metabolites, revealing their stronger attraction and ability to promote HCAR2 amino acid residue stability [97][98][99]. Similarly, the reduced RMSF of methylisocitric acid and tetradecanedioc acid bound to GABBR1 compared to metformin suggests less flexibility and stability (of the complexes) [35,44,93,95].…”

“…Various ligand-protein interactions were observed over the 120 ns MD simulation. The hydrogen bonds formed between a ligand and the protein target receptor determine the protein-ligand complex's stability [45,94,99]. Additionally, hydrogen bonds are indicative of a drug's specificity, metabolism, and adsorption [89].…”

“…Frontier molecular orbitals, namely, the LUMO and HOMO, are critical for identifying the chemical reaction of a system [106]. The energy gap between a molecule's HOMO and LUMO influences its chemical reactivity, kinetic stability, optical polarizability, and chemical hardnesssoftness [99,107]. In particular, the reactivity of a molecule exhibits a direct correlation with its energy gap, indicating that a molecule with smaller dimensions possesses a higher propensity to react with other molecular entities, such as proteins and enzymes [107].…”

“…The lower energy gap observed in ginsenoyne E, caffeic acid, and quinic acid against ADORA1, HCAR2, and GABBR1, respectively, suggests their high reactivities relative to other CS metabolites' reactivity (Table 4). Furthermore, molecules characterized by a larger energy gap tend to display enhanced hardness, reducing their reactivity [99,108]. The chemical hardness serves as a robust metric for evaluating the chemical stability of a molecule and plays a crucial role in investigations pertaining to drug design elucidations [36,99].…”

“…Furthermore, molecules characterized by a larger energy gap tend to display enhanced hardness, reducing their reactivity [99,108]. The chemical hardness serves as a robust metric for evaluating the chemical stability of a molecule and plays a crucial role in investigations pertaining to drug design elucidations [36,99]. Soft molecules are characterized by an elevated level of polarizability compared to hard molecules, primarily because of their reduced energy demand for excitation [108].…”