Molecular Dynamics of the tRNAAla Acceptor Stem: Comparison between Continuum Reaction Field and Particle-Mesh Ewald Electrostatic Treatments

Abstract

Molecular dynamics simulations with an explicit solvent model are used to investigate the effect of long-range electrostatic interactions on the structure and dynamics of a 22-nucleotide RNA hairpin in solution, the E. coli tRNA A l a minihelix 5p-GGGGCUC(UUCG)GAGCUCC(ACCA). Two different treatments of long-range electrostatics are compared: a continuum reaction field method (CRF; two 1.2 ns simulations) and the particle-mesh Ewald method (PME; one 2.5 ns simulation). The reaction field simulations are the first for an RNA solute. The simulations converge rapidly to within 1.5 A of each other and of the X-ray structure, despite two starting conformations (taken from the ensemble of NMR structures) that differ from each other by 3.3 A and from the X-ray structure by 1.3 and 2.1 A, respectively. After 1000 ps of one CRF simulation, the helix begins to unfold, with the first two base pairs opening. Except for the last part of this simulation, the RNA helical parameters and atomic fluctuations and the solvent structure around the G3.U16 wobble pair are all in good agreement with experiment and between simulations, whereas counterions are more ordered with PME than with CRF.