Computational Modeling of Molecular Structures Guided by Hydrogen-Exchange Data
Computational Modeling of Molecular Structures Guided by Hydrogen-Exchange Data
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DOI：
10.1021/jasms.1c00328
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发表时间：
2022-02-02
影响因子：
3.2
通讯作者：
Borysik，Antoni J.
中科院分区：
文献类型：
--
作者：
Devaurs，Didier;Antunes，Dinler A.;Borysik，Antoni J.
氢交换监测实验产生的数据几十年来一直用于分子结构研究。尽管氢交换本身的结构决定因素存在不确定性，但此类数据已成功帮助指导具有挑战性的分子系统（例如膜蛋白或大型大分子复合物）的结构建模。由于氢交换监测提供了溶液中分子动力学的信息，因此它可以补充所谓的综合建模方法中的其他实验技术。然而，氢交换数据通常仅用于定性评估计算建模工具产生的分子结构。在本文中，我们超越定性方法，调查了使用氢交换数据定量指导分子结构计算建模的各种范式。尽管已经提出了许多预测模型来将分子结构和氢交换联系起来，但没有一个模型被结构生物学界广泛接受。在这里，我们提出了在文献中可以找到的尽可能多的氢交换预测模型，目的是提供此类的第一个详尽列表。从纯粹基于结构的模型到所谓的分数总体模型或基于知识的模型，该领域相当广阔。我们希望这篇论文能够成为从业者的资源，让他们获得更广泛的领域视角，并指导研究定义更好的预测模型。这最终将提高氢交换监测和分子建模之间的协同作用。
Data produced by hydrogen-exchange monitoring experiments have been used in structural studies of molecules for several decades. Despite uncertainties about the structural determinants of hydrogen exchange itself, such data have successfully helped guide the structural modeling of challenging molecular systems, such as membrane proteins or large macromolecular complexes. As hydrogen-exchange monitoring provides information on the dynamics of molecules in solution, it can complement other experimental techniques in so-called integrative modeling approaches. However, hydrogen-exchange data have often only been used to qualitatively assess molecular structures produced by computational modeling tools. In this paper, we look beyond qualitative approaches and survey the various paradigms under which hydrogen-exchange data have been used to quantitatively guide the computational modeling of molecular structures. Although numerous prediction models have been proposed to link molecular structure and hydrogen exchange, none of them has been widely accepted by the structural biology community. Here, we present as many hydrogen-exchange prediction models as we could find in the literature, with the aim of providing the first exhaustive list of its kind. From purely structure-based models to so-called fractional-population models or knowledge-based models, the field is quite vast. We aspire for this paper to become a resource for practitioners to gain a broader perspective on the field and guide research toward the definition of better prediction models. This will eventually improve synergies between hydrogen-exchange monitoring and molecular modeling.