AN EFFECTIVE SOLVATION TERM BASED ON ATOMIC OCCUPANCIES FOR USE IN PROTEIN SIMULATIONS
AN EFFECTIVE SOLVATION TERM BASED ON ATOMIC OCCUPANCIES FOR USE IN PROTEIN SIMULATIONS
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DOI：
10.1080/08927029308022161
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发表时间：
1993-01-01
影响因子：
2.1
通讯作者：
SANDER, C
中科院分区：
文献类型：
--
作者：
STOUTEN, PFW;FROMMEL, C;SANDER, C
回顾了基于连续介质模型处理溶剂效应的几种方法，并提出并测试了一种基于占据原子体积（占用）的新方法。新方法用原子溶剂化参数描述蛋白质-水相互作用，原子溶剂化参数代表每单位体积的溶剂化自由能。使用实验溶剂化自由能确定六种不同原子类型的这些参数。该方法在 GROMOS 和 PRESTO 分子模拟程序套件中实现。使用溶剂化项的模拟比相应的真空模拟需要多 20-50% 的 CPU 时间，并且比显式水模拟快大约 20 倍。通过在水中、真空中和溶剂化项下进行 200 ps BPTI 模拟来测试方法和参数。通过将溶剂化模拟的结构和能量与来自几种 BPTI 晶体结构以及显式水和真空模拟的等效量进行比较来评估溶剂化项的性能。根据暴露的总表面、掩埋和暴露的极性表面、二级结构保存、氢键数量、能量贡献以及与 BPTI 晶体结构的位置偏差来评估模型结构。就所应用的所有标准而言，真空模拟产生了不切实际的结构。尽管部分二级结构溶解了，但用显性水模拟所得的结构更接近 5PTI 晶体结构。根据所有评估，使用有效溶剂化项的模拟产生的结构是正常的，并且在大多数方面与 5PTI 晶体结构非常相似，尽管在模拟过程中存在相当大的位置波动。已知模型和晶体结构不同的部分是灵活的，并且观察到的差异可能是物理上真实的。基于占用的有效溶剂化项不仅在计算机时间方面非常有效，而且还为 BPTI 带来了有意义的结构特性。因此，它通常可用于大分子的分子动力学。
Several approaches to the treatment of solvent effects based on continuum models are reviewed and a new method based on occupied atomic volumes (occupancies) is proposed and tested. The new method describes protein-water interactions in terms of atomic solvation parameters, which represent the solvation free energy per unit of volume. These parameters were determined for six different atoms types, using experimental free energies of solvation. The method was implemented in the GROMOS and PRESTO molecular simulation program suites. Simulations with the solvation term require 20-50% more CPU time than the corresponding vacuum simulations and are approximately 20 times faster than explicit water simulations. The method and parameters were tested by carrying out 200 ps simulations of BPTI in water, in vacuo, and with the solvation term. The performance of the solvation term was assessed by comparing the structures and energies from the solvation simulations with the equivalent quantities derived from several BPTI crystal structures and from the explicit water and vacuum simulations. The model structures were evaluated in terms of exposed total surface, buried and exposed polar surfaces, secondary structure preservation, number of hydrogen bonds, energy contributions, and positional deviations from BPTI crystal structures. Vacuum simulations produced unrealistic structures with respect to all criteria applied. The structures resulting from the simulations with explicit water were closer to the 5PTI crystal structure, although part of the secondary structure dissolved. The simulations with the effective solvation term produce structures that are normal according to all evaluations and in most respects are remarkably similar to the 5PTI crystal structure despite considerable positional fluctuations during the simulations. The segments where the model and crystal structures differ are known to be flexible and the observed difference may be physically realistic. The effective solvation term based on occupancies is not only very efficient in terms of computer time but also results in meaningful structural properties for BPTI. It may therefore be generally useful in molecular dynamics of macromolecules.