Graduate School of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.
Molecules. 2019 Jul 22;24(14):2653. doi: 10.3390/molecules24142653.
Water molecules play a key role in protein stability, folding, function and ligand binding. Protein hydration has been studied using free energy perturbation algorithms. However, the study of protein hydration without free energy calculation is also an active field of research. Accordingly, topological water network (TWN) analysis has been carried out instead of free energy calculation in the present work to investigate hydration of proteins. Water networks around 20 amino acids in the aqueous solution were explored through molecular dynamics (MD) simulations. These simulation results were compared with experimental observations. Water molecules from the protein data bank structures showed TWN patterns similar to MD simulations. This work revealed that TWNs are effected by the surrounding environment. TWNs could provide valuable clues about the environment around amino acid residues in the proteins. The findings from this study could be exploited for TWN-based drug discovery and development.
水分子在蛋白质稳定性、折叠、功能和配体结合中起着关键作用。已经使用自由能微扰算法研究了蛋白质水合作用。然而，不进行自由能计算而研究蛋白质水合作用也是一个活跃的研究领域。因此，在本工作中，拓扑水网络（TWN）分析被用来代替自由能计算来研究蛋白质的水合作用。通过分子动力学（MD）模拟探索了水溶液中 20 个氨基酸左右的水网络。将这些模拟结果与实验观察结果进行了比较。来自蛋白质数据库结构的水分子显示出与 MD 模拟相似的 TWN 模式。这项工作表明，TWN 受到周围环境的影响。TWN 可以为蛋白质中氨基酸残基周围的环境提供有价值的线索。这项研究的结果可以用于基于 TWN 的药物发现和开发。
