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With or without Me: The effect of a single methyl group on the free energies of functional and nonfunctional conformations of human mitochondrial lysine transfer RNA (tRNALys) has been studied. The stabilization of the three distinct conformations by Mg2+ ion binding and free energy changes resulting from methylation were characterized and revealed a preference for the functionally relevant cloverleaf-shaped tRNA form (see picture). (Graph Presented).