Abstract
Magnesium plays a critical role in the structure, dynamics, and function of RNA. The precise microscopic effect of chelated magnesium on RNA structure is yet to be explored. Magnesium is known to act through its diffuse cloud around RNA, through the outer sphere (water-mediated), inner sphere, and often chelated ion-mediated interactions. A mechanism is proposed for the role of experimentally discovered site-specific chelated magnesium ions on the conformational dynamics of SAM-I riboswitch aptamers in bacteria. This mechanism is observed with atomistic simulations performed in a physiological mixed salt environment at a high temperature. The simulations were validated with phosphorothioate interference mapping experiments that help to identify crucial inner-sphere Mg2+ sites prescribing an appropriate initial distribution of inner- and outer-sphere magnesium ions to maintain a physiological ion concentration of monovalent and divalent salts. A concerted role of two chelated magnesium ions is newly discovered since the presence of both supports the formation of the pseudoknot. This constitutes a logical AND gate. The absence of any of these magnesium ions instigates the dissociation of long-range pseudoknot interaction exposing the inner core of the RNA. A base triple is the epicenter of the magnesium chelation effect. It allosterically controls RNA pseudoknot by bolstering the direct effect of magnesium chelation in protecting the functional fold of RNA to control ON and OFF transcription switching.