Revolutionizing Diabetes Treatment: Computational Insights into 4- Hydroxy isoleucine Derivatives and Advanced Molecular Screening for Anti-Diabetic Compounds

Abstract

Background: The present study focuses on the importance of, a peculiar nonprotein amino acid 4-hydroxy isoleucine (4OHIle) as a constituent isolated from fenugreek (Trigonella foenum-graecum), which plays a vital role in the treatment of Diabetes mellitus. Here, we represent 4-hydroxy isoleucine derivatives has the ability to simulate insulin production and increase insulin sensitivity in diabetes mellitus targets. Objectives In this study, using computational methods we search for suitable drug like compounds that have similar ligand binding kinetics to target diabetes mellitus. Methods The top drug like compounds are selected based on computational methods such as Molecular Docking, Molecular Dynamic Simulation, Gibbs Free Energy calculations and Free Energy Landscape (FEL), shape based generative modelling for de novo drug design. Results Docking-based simulation screened out best 2 compounds against each targeted enzyme implicated in diabetes. Further, their dynamics studies reveal that the compounds 4-OHIL, 4-OHIL-4, 2R-3S-4R-4OHIL and 4-OHIL-Amide-2 were affirmed as the best inhibitors of respective enzyme targets. The best inhibitors are further optimised using generative model (Ligdream) Conclusion Anticipating the competitive inhibition of target protein expression in diabetes mellitus, we envision that the best inhibitors of respective enzyme targets. The findings from this current investigation carry significant modifications for the advancement in order to improve their potential to treat type 2 diabetes