Department of Material Sciences and Process Engineering, Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences Vienna, 1190 Vienna, Austria.
Department of Chemistry, University of Natural Resources and Life Sciences Vienna, 1190 Vienna, Austria.
Int J Mol Sci. 2019 Dec 19;21(1):30. doi: 10.3390/ijms21010030.
By using molecular dynamics simulations with an efficient enhanced sampling technique and in combination with nuclear magnetic resonance (NMR) spectroscopy quantitative structural information on α -2,8-linked sialic acids is presented. We used a bottom-up approach to obtain a set of larger ensembles for tetra- and deca-sialic acid from model dimer and trimer systems that are in agreement with the available J-coupling constants and nuclear Overhauser effects. The molecular dynamic (MD) simulations with enhanced sampling are used to validate the force field used in this study for its further use. This empowered us to couple NMR observables in the MD framework via J-coupling and distance restraining simulations to obtain conformations that are supported by experimental data. We used these conformations in thermodynamic integration and one-step perturbation simulations to calculate the free-energy of suggested helical conformations. This study brings most of the available NMR experiments together and supplies information to resolve the conflict on the structures of poly- α -2,8-linked sialic acid.
本文使用高效增强采样技术的分子动力学模拟，并结合核磁共振（NMR）光谱，提供了关于α-2,8 连接唾液酸的定量结构信息。我们采用自下而上的方法，从模型二聚体和三聚体系统中获得了一系列更大的四聚体和十聚体混合物的集合，这些集合与可用的 J 耦合常数和核 Overhauser 效应一致。增强采样的分子动力学（MD）模拟用于验证本研究中使用的力场，以便进一步使用。这使我们能够通过 J 耦合和距离约束模拟将 NMR 可观测量耦合到 MD 框架中，以获得实验数据支持的构象。我们使用这些构象进行热力学积分和一步扰动模拟，以计算所提出的螺旋构象的自由能。这项研究将大多数现有的 NMR 实验结合在一起，并提供了信息来解决关于多聚α-2,8 连接唾液酸结构的冲突。
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