Informatics in Medicine Unlocked (Jan 2024)
Spondias mombin flavonoids showed super-binder ability with downstream molecular targets of Parkinson's disease: A structural study
Abstract
Spondias mombin is a prominent botanical resource and has garnered recognition within folkloric therapy. Parkinson's disease (PD), characterized by dopaminergic neuron attrition in the substantia nigra, manifests as motor anomalies like tremors, rigidity, and bradykinesia. This study capitalizes on S. mombin's reservoir of 100 characterized phytocompounds and employs computational methodologies to interrogate their potential with 35 PD-associated target proteins. Employing a multifaceted approach, we engaged in molecular docking, ADMET predictions, Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) evaluations, Density Functional Theory (DFT), and Molecular Dynamic Simulations (MDS). This comprehensive framework facilitated insightful structural assessments and predictive analyses. Impressively, flavonoids hailing from S. mombin, including quercetin, catechin, ellagic acid, and epicatechin, showed optimal binding affinities for PD-related target proteins. Moreover, these identified ligands exhibited minimal signs of mutagenicity, tumorigenicity, or irritancy, except for quercetin, which displayed elevated tumorigenic potential. Notably, quercetin and dopamine exhibited varying band gap energies, with quercetin the lowest (3.63 eV) and dopamine the highest (5.76 eV) values. MDS result suggests a synergistic outcome based on the RMSD and RMSF graphs for quercetin highlighting it as the best of all including the co-ligand. In a collective sense, our findings present S. mombin as a promising reservoir of active pharmaceutical ingredients, warranting further exploration for novel PD therapeutic avenues. Consequently, this study underscores the enhanced efficacy of phyto-ligands sourced from S. mombin, advocating their optimization as potential drug candidates.
