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キーワード:
K-turn motif; G-A base pairs; molecular dynamics simulations; locally enhanced sampling; principal component analysis; molecular dynamics
要旨:
Upon binding to the 15.5K protein, two tandem-sheared G-A base pairs are formed in the internal loop of the kink turn motif of U4 snRNA (Kt-U4). We have reported that the folding of Kt-U4 is assisted by protein binding. Unstable interactions that contribute to a large opening of the free RNA (“k-e motion”) were identified using locally enhanced sampling molecular dynamics (LES-MD) simulations, results that agree with experiment. A detailed analysis of the simulations reveals that the k-e motion in Kt-U4 is triggered both by loss of G-A base pairs in the internal loop and backbone flexibility in the stems. Essential dynamics show that the loss of G-A base pairs is correlated along the first mode but anti-correlated along the third mode with the k-e motion. Moreover, when enhanced sampling was confined to the internal loop, the RNA adopted an alternative conformation characterized by a sharper kink, opening of G-A base pairs and, modified stacking interactions. Thus, loss of G-A base pairs is insufficient for achieving a large opening of the free RNA. These findings, supported by previously published RNA structure probing experiments, suggest that G-A base pair formation occurs upon protein binding, thereby stabilizing a selective orientation of the stems.
