Insights into Ligand Binding to PreQ1 Riboswitch Aptamer from Molecular Dynamics Simulations

Riboswitches play roles in transcriptional or translational regulation through specific ligand binding of their aptamer domains. Although a number of ligand-bound aptamer complex structures have been solved, it is important to know ligand-free conformations of the aptamers in order to understand the mechanism of specific binding by ligands. In this paper, preQ(1) riboswitch aptamer domain from Bacillus subtilis is studied by overall 1.5 mu s all-atom molecular dynamics simulations We found that the ligand-free aptamer has a stable state with a folded P1-L3 and open binding pocket. The latter forms a cytosine-rich pool in which the nucleotide C19 oscillates between close and open positions, making it a potential conformation for preQ(1) entrance. The dynamic picture further suggests that the specific recognition of preQ(1) by the aptamer domain is not only facilitated by the key nucleotide C19 but also aided and enhanced by other cytosines around the binding pocket. These results should help to understand the details of preQ(1) binding.