Binding Induced Switch For PreQ₁ Riboswitch With Dynamics Correlation Network

Riboswitches are a class of metabolism control elements mostly in bacteria. Some metabolites and ions have been found to bind with specific riboswitch to regulate the transcription and translation of associated genes. Prequeuosine(preQ1) is the last free precursor in the biosynthetic pathway of queuosine which is crucial for translation efficiency and fidelity. However, the regulation mechanism for preQ1 riboswitch is unsolved. Here we constructed nucleotide/nucleotide dynamics correlation network based on molecular dynamics simulation to reveal the regulation mechanism. The results suggest that the correlation network in bound riboswitch is distinctly different from that in apo state. Thus, a hypothesis of “preQ1 binding induced switch” is proposed to link riboswitch and translation regulation. These observations were further confirmed with the results from community analysis based on the Girvan-Newman algorithm and binding free energies. Finally, a possible regulation pathway of A35-A51-U10-A11-G12-G56 is also identified based on the analysis of the network for bound riboswitch and confirmed by nucleotide mutant and weaken modification. Interestingly, no similar pathways could be found in apo state. These combined network analysis methods can be used as general strategy in studies of riboswitch structure-function relationship.