Nonbonded Parameter Optimization Improving Simulation of Intrinsically Disordered Phosphoproteins

• DOI: 10.1021/acs.jcim.4c02248
• Publication Date: 2025-03-10T11:46:31Z
• Authors: Xinyao Zheng; Ge Song; Zhengxin Li; Bowen Duan; Bofan Zhu; Hai-Feng Chen
• Keywords: Intrinsically Disordered Proteins

Phosphorylated proteins play a crucial role in numerous cellular processes, acting as key regulators signal transduction networks, cell expansion, and various biochemical reactions. Molecular dynamics (MD) simulations are powerful tools for exploring the dynamic conformations of phosphoproteins. However, conventional force fields often underestimate radii gyration (Rg) To address this limitation, we reoptimized parameters vDW radius oxygen atom charge phosphorus with reweighting algorithm thermodynamic integration, named phosRg. Validation on test systems seven representative phosphoproteins demonstrates that phosRg has better agreement experiment Rg chemical shift than does phosaa10. Furthermore, generated more extensional fewer hydrophobic interactions hydrogen bonds At same time, found TIP4P-D solvent model is suitable choice to be used simulation phosphorylated proteins. These results indicate our dual-objective optimization strategy necessary improving parameters. In summary, should also other