Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Examining the Unusual Conformation of GAGU Internal Loop Using Molecular Dynamics
The RNA duplex containing internal loop AG/AG surrounded by GU/GU base pairs (5-'GAGU-3') 2 has two conformations in solution as measured by NMR spectroscopy. Major conformation has unusual structure of the internal loop consisting of trans-Watson-Crick/Hoogsteen GG pairs, two A residues stacked on each other and U residues flipped outside the helix (Kennedy et. al. 2012). This differs markedly from the AG/AG internal loops surrounded by canonical GC/GC, AU/AU or even UG/UG base pairs (5'-GAGC-3') 2 , (5'-AAGU-3')2 and (5'-UAGG-3') 2 which all form the expected structure where hydrogen bonding is maximized, i.e. cis-Watson-Crick/Watson-Crick AG hydrogen bonds (Hammond et al. 2010).
In this work molecular dynamics was used to investigate the stability and origin of GAGU duplex unusual conformation. Multiple long simulations were performed for the GAGU, GAGC, AAGU and UAGG duplexes in both native and alternative conformations using the Amber software package and the ff14SB RNA force field.
Results indicate that the Amber force field is able to correctly predict that the NMR conformation of GAGU is more stable than the alternative conformation that maximizes hydrogen bonding. The origin of this stability can be explained by the change of balance between electrostatic, van der Waals and solvation terms in the internal loop as the flanking bases are changed.
Hammond, N.B. et al, Biochemistry, 2010, 49, 5817-5827.
Department of Biochemistry & Biophysics