Informace o publikaci
How Binding Site Flexibility Promotes RNA Scanning by TbRGG2 RRM: A Molecular Dynamics Simulation Study
| Autoři | |
|---|---|
| Rok publikování | 2025 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Journal of Chemical Information and Modeling |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://pubs.acs.org/doi/full/10.1021/acs.jcim.4c01954 |
| Doi | http://dx.doi.org/10.1021/acs.jcim.4c01954 |
| Klíčová slova | RRM; Molecular Dynamics; TbRGG2; kRNA editing; Stafix |
| Popis | RNA recognition motifs (RRMs) are a key class of proteins that primarily bind single-stranded RNAs. In this study, we applied standard atomistic molecular dynamics simulations to obtain insights into the intricate binding dynamics between uridine-rich RNAs and TbRGG2 RRM using the recently developed OL3-Stafix AMBER force field, which improves the description of single-stranded RNA molecules. Complementing structural experiments that unveil a primary binding mode with a single uridine bound, our simulations uncover two supplementary binding modes in which adjacent nucleotides encroach upon the binding pocket. This leads to a unique molecular mechanism through which the TbRGG2 RRM is capable of rapidly transitioning the U-rich sequence. In contrast, the presence of non-native cytidines induces stalling and destabilization of the complex. By leveraging extensive equilibrium dynamics and a large variety of binding states, TbRGG2 RRM effectively expedites diffusion along the RNA substrate while ensuring robust selectivity for U-rich sequences despite featuring a solitary binding pocket. We further substantiate our description of the complex dynamics by simulating the fully spontaneous association process of U-rich sequences to the TbRGG2 RRM. Our study highlights the critical role of dynamics and auxiliary binding states in interface dynamics employed by RNA-binding proteins, which is not readily apparent in traditional structural studies but could represent a general type of binding strategy employed by many RNA-binding proteins. |