FisMat2017 - Submission - View

Abstract's title: Combining simulations and solution experiments as a paradigm for RNA force field refinement
Submitting author: Andrea Cesari
Affiliation: SISSA
Affiliation Address: Via Bonomea, 265, 34136, Trieste
Country: Italy
Oral presentation/Poster (Author's request): Oral presentation
Other authors and affiliations: Alejandro Gil Ley (SISSA) Giovanni Bussi (SISSA)

RNA structure and dynamics play a fundamental role in non-coding RNAs and significantly affect functions such as gene expression inhibition, splicing and catalysis. Molecular dynamics is a computational tool that can be in principle used to investigate RNA structure and dynamics at atomistic resolution. However, its capability to predict and explain experimental data is limited by the accuracy of the employed potential energy functions, also known as force fields. Recent works have shown that state-of-the-art force fields could predict unphysical conformations that are not in agreement with experiments. [1-3] The emerging strategy to overcome these limitations is to complement molecular dynamics with experimental data included as restraints. [4,5] Solution NMR data are particularly useful since they provide averages over the conformations explored on the experimental time scale and ultimately give access to RNA dynamics. We propose a scheme based on the maximum entropy principle to combine bulk experiments with molecular dynamics simulations explicitly taking into account experimental errors[6,7]. The method is applied to a set of nucleosides and dinucleotides in a chemically-consistent manner, allowing for portable corrections, and suggests a new paradigm for force field refinement.
1. Bergonzo et al., RNA 2015
2. Kuhrová et al., JCTC 2016
3. Bottaro et al., JPCL 2016
4. Cavalli et al., JCP 2013
5. Hummer et al., JCP 2015
6. Pitera et al., JCTC 2012
7. Cesari et al., JCTC 2016