Assessing RNA atomistic force fields via energy landscape explorations in implicit solvent.

IF 4.9 Q1 BIOPHYSICS
Biophysical reviews Pub Date : 2024-06-17 eCollection Date: 2024-06-01 DOI:10.1007/s12551-024-01202-9
Konstantin Röder, Samuela Pasquali
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引用次数: 0

Abstract

Predicting the structure and dynamics of RNA molecules still proves challenging because of the relative scarcity of experimental RNA structures on which to train models and the very sensitive nature of RNA towards its environment. In the last decade, several atomistic force fields specifically designed for RNA have been proposed and are commonly used for simulations. However, it is not necessarily clear which force field is the most suitable for a given RNA molecule. In this contribution, we propose the use of the computational energy landscape framework to explore the energy landscape of RNA systems as it can bring complementary information to the more standard approaches of enhanced sampling simulations based on molecular dynamics. We apply the EL framework to the study of a small RNA pseudoknot, the Aquifex aeolicus tmRNA pseudoknot PK1, and we compare the results of five different RNA force fields currently available in the AMBER simulation software, in implicit solvent. With this computational approach, we can not only compare the predicted 'native' states for the different force fields, but the method enables us to study metastable states as well. As a result, our comparison not only looks at structural features of low energy folded structures, but provides insight into folding pathways and higher energy excited states, opening to the possibility of assessing the validity of force fields also based on kinetics and experiments providing information on metastable and unfolded states.

Supplementary information: The online version contains supplementary material available at 10.1007/s12551-024-01202-9.

通过隐含溶剂中的能量景观探索评估 RNA 原子力场
由于可用于训练模型的实验 RNA 结构相对稀缺,而且 RNA 对其环境非常敏感,因此预测 RNA 分子的结构和动力学仍然具有挑战性。在过去十年中,已经提出了几种专门为 RNA 设计的原子力场,并普遍用于模拟。然而,对于特定的 RNA 分子,哪种力场最合适并不一定明确。在这篇论文中,我们建议使用计算能谱框架来探索 RNA 系统的能谱,因为它可以为基于分子动力学的增强采样模拟这种更标准的方法提供补充信息。我们将 EL 框架应用于研究一种小 RNA 伪结节--Aquifex aeolicus tmRNA 伪结节 PK1,并比较了 AMBER 模拟软件中目前可用的五种不同 RNA 力场在隐式溶剂中的结果。通过这种计算方法,我们不仅可以比较不同力场预测的 "原生 "状态,而且还能研究可迁移状态。因此,我们的比较不仅考察了低能折叠结构的特征,还深入了解了折叠途径和高能激发态,为评估力场的有效性提供了可能,同时也为动力学和实验提供了有关蜕变态和展开态的信息:在线版本包含补充材料,可查阅 10.1007/s12551-024-01202-9。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biophysical reviews
Biophysical reviews Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
8.90
自引率
0.00%
发文量
93
期刊介绍: Biophysical Reviews aims to publish critical and timely reviews from key figures in the field of biophysics. The bulk of the reviews that are currently published are from invited authors, but the journal is also open for non-solicited reviews. Interested authors are encouraged to discuss the possibility of contributing a review with the Editor-in-Chief prior to submission. Through publishing reviews on biophysics, the editors of the journal hope to illustrate the great power and potential of physical techniques in the biological sciences, they aim to stimulate the discussion and promote further research and would like to educate and enthuse basic researcher scientists and students of biophysics. Biophysical Reviews covers the entire field of biophysics, generally defined as the science of describing and defining biological phenomenon using the concepts and the techniques of physics. This includes but is not limited by such areas as: - Bioinformatics - Biophysical methods and instrumentation - Medical biophysics - Biosystems - Cell biophysics and organization - Macromolecules: dynamics, structures and interactions - Single molecule biophysics - Membrane biophysics, channels and transportation
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