Xia Bin, Tsui Vickie, Case David A, Dyson H Jane, Wright Peter E
Department of Molecular Biology and Skaggs Intitute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92122, USA.
J Biomol NMR. 2002 Apr;22(4):317-31. doi: 10.1023/a:1014929925008.
The inclusion of explicit solvent water in molecular dynamics refinement of NMR structures ought to provide the most physically meaningful accounting for the effects of solvent on structure, but is computationally expensive. In order to evaluate the validity of commonly used vacuum refinements and of recently developed continuum solvent model methods, we have used three different methods to refine a set of NMR solution structures of a medium sized protein, Escherichia coli glutaredoxin 2, from starting structures calculated using the program DYANA. The three different refinement protocols used molecular dynamics simulated annealing with the program AMBER in vacuum (VAC), including a generalized Born (GB) solvent model, and a full calculation including explicit solvent water (WAT). The structures obtained using the three methods of refinements were very similar, a reflection of their generally well-determined nature. However, the structures refined with the generalized Born model were more similar to those from explicit water refinement than those refined in vacuum. Significant improvement was seen in the percentage of backbone dihedral angles in the most favored regions of phi, psi space and in hydrogen bond pattern for structures refined with the GB and WAT models, compared with the structures refined in vacuum. The explicit water calculation took an average of 200 h of CPU time per structure on an SGI cluster, compared to 15-90 h for the GB calculation (depending on the parameters used) and 2 h for the vacuum calculation. The generalized Born solvent model proved to be an excellent compromise between the vacuum and explicit water refinements, giving results comparable to those of the explicit water calculation. Some improvement for phi and psi angle distribution and hydrogen bond pattern can also be achieved by energy minimizing the vacuum structures with the GB model, which takes a much shorter time than MD simulations with the GB model.
在核磁共振（NMR）结构的分子动力学精修中纳入明确的溶剂水，理应能为溶剂对结构的影响提供最具物理意义的解释，但计算成本高昂。为了评估常用的真空精修方法以及最近开发的连续介质溶剂模型方法的有效性，我们使用了三种不同方法，对一组中等大小蛋白质（大肠杆菌谷氧还蛋白2）的NMR溶液结构进行精修，起始结构由DYANA程序计算得出。三种不同的精修方案使用AMBER程序在真空（VAC）中进行分子动力学模拟退火，其中包括广义玻恩（GB）溶剂模型，以及包含明确溶剂水的完整计算（WAT）。使用这三种精修方法得到的结构非常相似，这反映出它们总体上结构确定良好的性质。然而，用广义玻恩模型精修的结构比在真空中精修的结构更类似于用明确水精修得到的结构。与在真空中精修的结构相比，用GB和WAT模型精修的结构在φ、ψ空间最有利区域的主链二面角百分比以及氢键模式方面有显著改善。在SGI集群上，明确水计算每个结构平均需要200小时的CPU时间，而GB计算需要15 - 90小时（取决于所使用的参数），真空计算则需要2小时。广义玻恩溶剂模型被证明是真空精修和明确水精修之间的绝佳折衷方案，其结果与明确水计算相当。通过用GB模型对真空结构进行能量最小化，也可以在φ和ψ角分布以及氢键模式方面实现一些改进，这比用GB模型进行分子动力学模拟所需时间短得多。
