Reproducing kernel potential energy surfaces in biomolecular simulations: Nitric oxide binding to myoglobin

Multidimensional potential energy surfaces based on reproducing kernel-interpolation are employed to explore the energetics and dynamics of free and bound nitric oxide in myoglobin (Mb). Combining a force field description for the majority of degrees of freedom and the higher-accuracy representation for the NO ligand and the Fe out-of-plane motion allows for a simulation approach akin to a mixed quantum mechanics/molecular mechanics treatment. However, the kernel-representation can be evaluated at conventional force-field speed. With the explicit inclusion of the Fe-out-of-plane (Fe-oop) coordinate, the dynamics and structural equilibrium after photodissociation of the ligand are correctly described compared to experiment. Experimentally, the Fe-oop coordinate plays an important role for the ligand dynamics. This is also found here where the isomerization dynamics between the Fe-ON and Fe-NO state is significantly affected whether or not this co-ordinate is explicitly included. Although the Fe-ON conformation is metastable when considering only the bound A state, it may disappear once the A state is included. This explains the absence of the Fe-ON state in previous experimental investigations of MbNO.