Polarizable and fixed-charge force fields give qualitatively different pictures of how chorismate mutase pre-organizes its substrate for catalysis
- Molecular dynamics of chorismate mutase were run with the polarizable AMOEBA force field and the fixed-charge AMBER force field, then compared.
- Only AMOEBA let the substrate visit reactive, transition-state-like geometries, and the two models produced different active-site hydrogen-bond networks and electric fields.
- A control with induced dipoles switched off pinpointed explicit polarization as the cause; the work is a computational comparison without experimental validation.
💡 Points Based on the abstract
That AMOEBA samples reactive geometries and AMBER does not is intriguing, yet it proves little on its own: a polarizable model can over-stabilize near-transition-state conformers as easily as it corrects a fixed-charge bias. What is missing is a comparison with experiment, such as a QM/MM barrier or kcat shifts in known mutants. For now it argues for budgeting polarizable runs on electrostatics-driven targets, not for a verdict.
Polarization Is Required to Model Electrostatic Preorganization: The Case of Chorismate Mutase ↗