Molecular dynamics simulation of the binding process of ligands to the add adenine riboswitch aptamer.

Riboswitches are RNA-structured elements that modulate gene expression through changing their conformation in response to specific metabolite binding. However, the regulation mechanisms of riboswitches by ligand binding are still not well understood. At present two possible ligand-binding mechanisms have been proposed: conformational selection and induced fit. Based on explicit-solvent molecular dynamics (MD) simulations, we have studied the process of the binding of ligands (adenines) to add adenine riboswitch aptamer (AARA) in detail. Our results show that the relative high flexibility of the junction J23 of AARA allows the ligands to be captured by the binding pocket of AARA in a near-native state, which may be driven by hydrophobic and base-stacking interactions. In addition, the binding of a ligand makes the stem P1 and the junction J23 of AARA more stable than in the absence of the ligand. Generally, our analyses show that the ligand-binding process of the add adenine riboswitch may be partially embodied by a conformational selection mechanism.