Developing Force Fields for Accurate Mg2+ and Triphosphate Interactions in ATP∙Mg2+ Complexes

In cells, adenosine triphosphate(ATP) and guanosine triphosphate(GTP) molecules typically form tri-coordinated or bi-coordinated ATP∙Mg2+ or GTP∙Mg2+ complexes with Mg2+ ions and bind to proteins, participating in and regulating many important cellular functions. The accuracy of their force field parameters plays a crucial role in studying the function-related conformations of ATP∙Mg2+ or GTP∙Mg2+ using molecular dynamics (MD) simulations. The parameters developed based on the methyl triphosphate model in existing AMBER force fields cannot accurately describe the conformational distribution of tri-coordinated or bi-coordinated ATP∙Mg2+ or GTP∙Mg2+ complexes in solution. In this study, we develop force field parameters for the triphosphate group based on the new ribosyl triphosphate model, considering dihedral coupling effect, accurate van der Waals (vdW) interactions, and the influence of strongly polarized charges on conformational balance. The new parameters can accurately describe the conformational balance of tri-coordinated and bi-coordinated ATP∙Mg2+ or GTP∙Mg2+ conformations in solution and can be applied to simulate protein kinase.