Molecular Dynamics Simulations of Protein RNA Complexes by Using an Advanced Electrostatic Model

Protein–RNA interactions are integral to the biological
functions of RNA. It is well recognized that molecular dynamics (MD)
simulations of protein–RNA complexes are more challenging than
those of each component. The difficulty arises from the strong electrostatic
interactions and the delicate balance between various types of physical
forces at the interface. Previously, MD simulations of protein–RNA
complexes have predominantly employed fixed-charge force fields. Although
force field modifications have been developed to address problems
identified in the simulations, some protein–RNA structures
are still hard to reproduce by simulations. Here, we present MD simulations
of two representative protein–RNA complexes using the AMOEBA
polarizable force field. The van der Waals parameters were refined
to reproduce accurate quantum-mechanical data of base–base
and base–amino acid interactions. It was found that the refined
parameters produced a more stable hydrogen-bond network in the interface.
One of the complexes remained stable during the short simulations,
whereas it could quickly break down in previous simulations using
fixed-charge force fields. There was reversible breaking and formation
of hydrogen bonds that are observed in the crystal structure, which
may indicate the difference in solution and crystal structures. While
further improvement and validation of the force fields are still needed,
this work demonstrates that polarizable force fields are promising
for the study of protein–RNA complexes.