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Center for Nonlinear Studies |
Ribonucleic acid (RNA) is acquiring a large importance in cell biology, as more functions that it accomplishes are discovered. However, experimental characterization of RNAs dynamical behavior at atomistic level is difficult. Molecular simulations at atomistic detail, in combination with state-of-the-art free-energy techniques and advanced analysis protocols, could in principle bridge the gap providing an unparalleled perspective on the mechanism and dynamics of RNA folding and conformational transitions. However, current empirical force fields used to model RNA are not yet accurate enough to predict structural dynamics in agreement with solution phase experiments. I will here show how the maximum entropy principle can be used to optimally combine molecular simulations and experimental data [1]. Applications of these approaches to the determination of RNA structural dynamics based on NMR data will be presented, ranging from short oligonucleotides [2] to larger biologically relevant non-coding RNAs [3,4]. I will also show how experimental data can be used for systematic force-field refinement [5]. Finally, I will discuss our recent efforts to link RNA structure and chemical probing data [6]. [1] Cesari, Reisser, Bussi, Computation (2018) [2] Bottaro, Bussi, Kennedy, Turner, and Lindorff-Larsen, Sci. Adv. (2018) [3] Podbevsek et al, Sci. Rep. (2018) [4] Reisser et al, in preparation [5] Cesari, Bottaro, Bussi, et al, in preparation [6] Mlynsky and Bussi, JPCL (2018)
Host: Angel Garcia