Role of ligand binding in structural organization of add A-riboswitch aptamer: a molecular dynamics simulation

The specific binding of ligands is the first step of gene expression or translation regulation by riboswitches. However, understanding the mechanism of the specific binding is still difficult because the tertiary structures of the riboswitch aptamers are available almost only for ligand-bound state at present. In this paper we hope to give some insights into this problem through the studies of the role of ligand-aptamer interaction in the structural organization of add A-riboswitch aptamer, based on the crystal structure of the ligand-bound aptamer. We use all-atom molecular dynamics to simulate the behaviors of the aptamer in ligand-bound, free and mutated states by Amber force field. The results show that the correct paring of the ligand adenine with the nucleotide U74 in the binding pocket is crucial to stabilizing the conformations of the ligand-bound aptamer, especially the helix P1 connecting the expression platform. Our results also suggest that both the nucleotide U74 and U51 may be the key sites of the ligand recognition but the former has much higher probability as the initial docking site. This is in agreement with previous experimental results.