Development of Site-Specific Mg2+–RNA Force Field Parameters: A Dream or Reality? Guidelines from Combined Molecular Dynamics and Quantum Mechanics Simulations

摘要: The vital contribution of Mg2+ ions to RNA biology is challenging dissect at the experimental level. This calls for integrative support atomistic simulations, which classical level are plagued by limited accuracy. Indeed, force fields intrinsically neglect nontrivial electronic effects that exerts on its surrounding ligands in varying coordination environments. Here, we present a combined computational study based molecular dynamics (MD) and Density Functional Theory (DFT) calculations, aimed characterizing (i) performance five field (FF) models systems (ii) how charge transfer polarization affect binding different motifs. As result, total ∼2.5 μs MD simulations (100/200 ns each run) two prototypical Mg2+-dependent ribozymes showed remarkable differences terms populations inner-sphere site types. Most importantly, complementary DFT calculations unveiled diff...