Computational investigation of nanoemulsion-released tocopherol for treating cardiovascular diseases: Insights from molecular dynamic simulation and deep learning prediction

Abstract

This research investigated the potential of tocopherol released from nanoemulsion as a therapeutic agent for cardiovascular diseases (CVD) through comprehensive in-silico site-specific molecular docking analysis and AI- driven Molecular Dynamic Simulation, between tocopherol and seven CVD-related proteins (Angiotensin Converting Enzyme (ACE) (1O8a), Human Angiotensin Receptor (4YAY), P38 Mitogen-Activated Protein Kinase (MAPK) (4DLI), HMG-CoA Reductase (1HW9), β-1-Adrenergic Receptor (2YCW), Human C-reactive Protein (1BO9), and Cyclooxygenase-2 (1CX2)). Our findings revealed significant interactions. α-Tocopherol exhibited strong binding affinities, particularly with the 2YCW protein, evidenced by a Vina score of -11.9 ± 0.86 kcal/mol and an inhibition constant of 1.4 ± 0.12 µM. Extensive hydrophobic interactions and significant hydrogen bonds were identified as critical for the stability of these complexes. Furthermore, Molecular Dynamics (MD) simulations, RMSD, Rg, RMSF, and Free Energy Landscape (FEL) profiles, and a deep convolutional neural network (CNN) used for predicting interaction sites from protein sequences, illustrated that the protein-ligand complexes attained dynamic configuration stability with RMSD values converging around 0.3 nm, underscoring the robustness of tocopherol-protein interactions. The pathway analysis highlights the possibility of tocopherol's involvement in interacting with several key biological pathways, Dilated Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, Hypertrophic Cardiomyopathy, and Apoptosis.This study revealed significant insights into the interactions of Nanoemulsion-released tocopherol with key proteins involved in the development of cardiovascular diseases, aimed at improving cardiovascular health. However, the findings of the study require meticulous experimental study and clinical trials to provide accurate results and validate tocopherol's therapeutic efficacy.