Comparison of molecular dynamics and harmonic mode calculations on RNA

Conformational fluctuations of a double-stranded RNA oligonucleotide have been calculated from a two nanosecond molecular dynamics simulation including explicit waters and ions and from a harmonic mode analysis. The harmonic mode analysis was performed in the absence of solvent using various effective dielectric screening functions. RNA flexibility was analyzed and compared at the level of atomic position fluctuations, helical base-pair descriptor fluctuations and global helix bending, stretching, and twisting flexibilities. Although quantitative differences were found, the qualitative pattern of atomic position and helical descriptor fluctuations along the sequence was similar for both methods. For the helical descriptor flexibility, the largest differences were observed for base-pair roll and rise that showed two times larger fluctuations in the molecular dynamics simulation. A significant overlap between the sub-space spanned by soft principal components calculated from the molecular dynamics simulation and harmonic modes was found. Both approaches predict a negative covariation for most helical base-pair step descriptors of neighboring base pair steps (with the exception of rise), which tend to stiffen the RNA at the global level. The RNA persistence length extracted from the molecular dynamics simulation (350-600 A) is smaller than the experimental value ( approximately 720 A) and estimates based on the harmonic mode approach (1100-1700 A).