Dynamics differences of SAM‐I riboswitch aptamer between SAM bound and without SAM: insight into conformational rearrangement

Abstract

Increasing attention has focused on targeting RNAs for small molecule drug design. However, because RNAs are highly flexible, it is still not clear how the interactions between small molecules and RNAs are coupled with the conformational change of RNAs. A riboswitch is an autonomous cis‐regulatory element that controls gene expression in response to the signals from small molecule metabolites, such as amino acids, nucleotides, or enzyme cofactors etc. The SAM‐I riboswitch is one member of this regulatory family that can control the expression of biosynthetic proteins involved in sulfur metabolism through conformational change upon the binding of S‐adenosylmethione (SAM). Although the structure of SAM‐I riboswitch aptamer domain has been solved via X‐ray crystallography, it is just a static view of how SAM binds to SAM‐I riboswitch. In this study, molecular dynamics (MD) simulations are performed on SAM‐I riboswitch aptamer with SAM and without SAM. Principle component analysis (PCA) is applied to explore the global dynamics differences of SAM‐I riboswitch aptamer between SAM present and SAM absent. Additionally, other trajectory analyses are also used to probe the correlation between the local flexibility and the global motion. MD simulation results suggest that dynamics of the P4 helix is affected upon the binding of SAM. This change in dynamic behavior may be related to the conformational changes observed in the SAM‐I riboswitch.