Tian Ye, Schwieters Charles D, Opella Stanley J, Marassi Francesca M
Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0307, USA.
Division of Computational Bioscience, Building 12A, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892-5624, USA.
J Magn Reson. 2014 Jun;243:54-64. doi: 10.1016/j.jmr.2014.03.011. Epub 2014 Apr 2.
The benefits of protein structure refinement in water are well documented. However, performing structure refinement with explicit atomic representation of the solvent molecules is computationally expensive and impractical for NMR-restrained structure calculations that start from completely extended polypeptide templates. Here we describe a new implicit solvation potential, EEFx (Effective Energy Function for XPLOR-NIH), for NMR-restrained structure calculations of proteins in XPLOR-NIH. The key components of EEFx are an energy term for solvation energy that works together with other nonbonded energy functions, and a dedicated force field for conformational and nonbonded protein interaction parameters. The initial results obtained with EEFx show that significant improvements in structural quality can be obtained. EEFx is computationally efficient and can be used both to fold and refine structures. Overall, EEFx improves the quality of protein conformation and nonbonded atomic interactions. Moreover, such benefits are accompanied by enhanced structural precision and enhanced structural accuracy, reflected in improved agreement with the cross-validated dipolar coupling data. Finally, implementation of EEFx calculations is straightforward and computationally efficient. Overall, EEFx provides a useful method for the practical calculation of experimental protein structures in a physically realistic environment.
蛋白质在水中进行结构优化的益处已有充分记录。然而，对于从完全伸展的多肽模板开始的核磁共振约束结构计算而言，使用溶剂分子的显式原子表示进行结构优化在计算上成本高昂且不切实际。在此，我们描述了一种新的隐式溶剂化势EEFx（用于XPLOR-NIH的有效能量函数），用于在XPLOR-NIH中对蛋白质进行核磁共振约束结构计算。EEFx的关键组成部分包括一个与其他非键合能量函数协同作用的溶剂化能量项，以及一个用于构象和非键合蛋白质相互作用参数的专用力场。使用EEFx获得的初步结果表明，结构质量可得到显著改善。EEFx在计算上效率很高，可用于折叠和优化结构。总体而言，EEFx提高了蛋白质构象和非键合原子相互作用的质量。此外，这些益处伴随着更高的结构精度和准确性，这体现在与交叉验证的偶极耦合数据的更好一致性上。最后，EEFx计算的实现简单且计算效率高。总体而言，EEFx为在物理现实环境中实际计算实验性蛋白质结构提供了一种有用的方法。
