Multiscale study demonstrates that local environment and binding angle influence acylation reactions in RNA molecules, suggesting oxyanion formation is unnecessary.
Our findings emphasize the critical role of the local environment in facilitating the recruitment and proper accommodation of the SHAPE probe. All-atom umbrella sampling (US) molecular dynamics (MD) simulations underscored the significance of the binding angle in forming the pre-reactive complex, which was thoroughly analyzed using geometrical descriptors. In US QM/MM simulations, we used different initial structures to demonstrate the impact of favorable binding on the acylation reaction by characterizing the first step. Moreover, we investigated the deprotonation of the hydroxyl and its role in the acylation reaction, highlighting the role of the local environment and the probe proximity in this process. Our results suggest that the formation of oxyanion prior to the binding is not required to initiate the chemical reaction.
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Hognon et al. (2025) studied this question.
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