Comparative analysis of three-pillared and four-pillared synthetic glucose receptor using molecular dynamics simulations: a case study

The advancement of computational molecular modeling has significantly enhanced the development of synthetic glucose receptors, addressing one of the most challenging problems in glucose recognition. This study explores the design and analysis of both three-pillared and four-pillared synthetic glucose receptors. Using polar (1,2-Bis(3-methylureido)benzene) pillars combined with benzene, biphenyl, and phenanthrene fragments as apolar surfaces, we have designed novel receptors. Our molecular dynamics simulations reveal that benzene is the most favorable apolar fragment for creating synthetic glucose receptors. Further simulations incorporating Mesitylene, Trimethylmesitylene, Triethylmesitylene, and Triptopylmesitylene as apolar fragments with (1,2-Bis(3-methylureido)benzene) polar pillars demonstrate that receptors with Triethylmesitylene and Triptopylmesitylene exhibit stable conformations. Synthetic glucose receptors represent the future of therapeutics for glucose-related disorders and conditions. These receptors have wide-ranging applications, including functioning as glucose carriers and glucose extractors. The 3D structures of the receptors were constructed using the 3D Builder tool, followed by energy minimization <i>via</i> the MacroModel application. The glucose-receptor interaction poses were predicted using the GLIED tool. Calculations were performed using the Berendsen thermostat and barostat. Molecular dynamics (MD) simulations were conducted with the Langevin ensemble method, utilizing GPU-based DESMOND software with the OPLS2005 force field and the TIP3P solvent model.