Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size.
Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size.
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DOI：
10.7554/elife.35560
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发表时间：
2018-07-12
期刊：
影响因子：
7.7
通讯作者：
Karplus M
中科院分区：
文献类型：
--
作者：
El Hage K;Hédin F;Gupta PK;Meuwly M;Karplus M
最近对人血红蛋白(Hb)的分子动力学(MD)模拟得到的结果与实验不符。虽然已知无配体(T)和有配体(R)四聚体在溶液中是稳定的，但已发表的分子动力学模拟T经历了一个快速的四元转变为类R结构。我们证明，只有当周期溶剂盒包含的水分子比此类模拟的标准尺寸多十倍时，T才是稳定的。结果表明，要表现出稳定T四聚体的疏水效应，需要这样一个大的盒子。即使在最大的盒子里，T也是不稳定的，除非他的146是质子化的，这提供了对佩鲁茨模型的原子验证。在评估各种系统的现有和未来模拟时，必须考虑到需要超大盒子才能获得有意义的结果的可能性。
Recent molecular dynamics (MD) simulations of human hemoglobin (Hb) give results in disagreement with experiment. Although it is known that the unliganded (T) and liganded (R) tetramers are stable in solution, the published MD simulations of T undergo a rapid quaternary transition to an R-like structure. We show that T is stable only when the periodic solvent box contains ten times more water molecules than the standard size for such simulations. The results suggest that such a large box is required for the hydrophobic effect, which stabilizes the T tetramer, to be manifested. Even in the largest box, T is not stable unless His146 is protonated, providing an atomistic validation of the Perutz model. The possibility that extra large boxes are required to obtain meaningful results will have to be considered in evaluating existing and future simulations of a wide range of systems.