Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Simulation of RNA Tandem GA base pairs provides insights about the forces behind conformational preference
Conformational changes are important for RNA function. We used molecular mechanics with all-atom models to understand conformational preference in RNA tandem guanine-adenine (GA) base pairs. These tandem GA base pairs play important roles in determining the stability and structural dynamics of RNA tertiary structures. Previous solution structures showed that these tandem GA base pairs adopt either imino (cis-Watson-Crick/cis-Watson-Crick interaction) or sheared (trans-Hoogsteen/trans-Hoogsteen interaction) pairing depending on the sequence and orientation of the adjacent base pairs. In our simulations we modeled (GCGGACGC)2 (Wu and Turner 1996) and (GCGGAUGC)2 (Tolbert et al., 2007) experimentally preferred as imino and sheared respectively. Besides the experimentally preferred conformation, we constructed models of the non-native conformations by changing cytosine to uracil or uracil to cytosine. We used explicit solvent molecular dynamics and free energy calculation with umbrella sampling to measure the free energy deference of the experimentally preferred conformation and the non-native conformations. A modification to ff10 required, which allowed the guanine bases’ amino group to leave the base plane (Yildirim et al., 2009). With this modification, the RMSD of unrestrained simulations and the free energy surfaces are improved, suggesting the importance of electrostatic interactions by G amino groups in stabilizing the native structures.
Figures, left to right RMSD as a function of time for ff10, RMSD as a function of time for modified ff10, two-dimensional free energy surface with ff10 and two-dimensional free energy surface with modified ff10.
David H. Mathews
Department of Biochemistry & Biophysics and Center for RNA Biology
University of Rochester Medical Center