Molecular Modulation of the SAM-I Riboswitch Drives Global Dynamical Shifts

Simulations show the SAM-I riboswitch binds SAM, SAH, and JS4 differently, with ligand-specific local and distal effects that can shift riboswitch conformations.

• Why it matters: Protein-targeting antibiotics are increasingly ineffective, so RNA-based therapies need clearer molecular understanding of how riboswitches interact with both natural ligands and candidate binders.
• What they did: The study simulated interactions of the SAM-I riboswitch with its natural ligand SAM, the non-regulating analog SAH, and the virtual-screening candidate JS4, comparing local and distal binding behaviors.
• The result: The ligand-dependent binding patterns and potential conformational changes provide mechanistic insight to guide design of more effective RNA-targeting therapeutics.

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