Comparison of Secondary Structure Formation Using 10 Different Force Fields in Microsecond Molecular Dynamics Simulations.
Comparison of Secondary Structure Formation Using 10 Different Force Fields in Microsecond Molecular Dynamics Simulations.
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DOI：
10.1021/ct300323g
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发表时间：
2012-08-14
影响因子：
5.5
通讯作者：
Karttunen, Mikko
中科院分区：
文献类型：
--
作者：
Cino, Elio A.;Choy, Wing-Yiu;Karttunen, Mikko
我们比较了分子动力学（MD）模拟的β-发夹形成肽来自蛋白质Nrf 2与10个生物分子力场使用轨迹至少1 μs。总的模拟时间为37.2 μs。以前的研究表明，不同的力场，水模型，模拟方法和参数会影响模拟结果。使用Amber ff 99 SB-ILDN、Amber ff 99 SB *-ILDN、Amber ff 99 SB、Amber ff 99 SB *、Amber ff 03、Amber ff 03 *、GROMOS 96 43 a1 p、GROMOS 96 53 a6、CHARMM 27和OPLS-AA/L力场，在显式溶剂中用16聚体Nrf 2 β-发夹形成肽进行MD模拟。还研究了电荷基团、末端加帽和磷酸化对肽折叠的影响。尽管使用相同的起始结构和模拟参数，我们观察到各种力场之间的明显差异，甚至在使用相同力场的重复之间。我们的模拟表明，当使用Amber ff 99 SB-ILDN、Amber ff 99 SB *-ILDN、Amber ff 99 SB、Amber ff 99 SB *、Amber ff 03、Amber ff 03 *、GROMOS 96 43 a1 p或GROMOS 96 53 a6时，未加帽的肽在310 K下折叠成天然样β-发夹结构。CHARMM 27模拟能够在一些高温模拟中形成天然发夹，而OPLS-AA/L模拟在任何测试温度下都不产生天然发夹结构。使用电荷基团或肽封端基团的模拟与具有单原子电荷基团的未封端对应物没有很大不同。另一方面，位于β-转角的苏氨酸残基的磷酸化显著影响发夹的形成。据我们所知，这是第一次研究比较如此大的一组力场与β-发夹折叠。这种全面的比较将为其他进行类似模拟的人提供有益的指导。
We have compared molecular dynamics (MD) simulations of a β-hairpin forming peptide derived from the protein Nrf2 with 10 biomolecular force fields using trajectories of at least 1 μs. The total simulation time was 37.2 μs. Previous studies have shown that different force fields, water models, simulation methods, and parameters can affect simulation outcomes. The MD simulations were done in explicit solvent with a 16-mer Nrf2 β-hairpin forming peptide using Amber ff99SB-ILDN, Amber ff99SB*-ILDN, Amber ff99SB, Amber ff99SB*, Amber ff03, Amber ff03*, GROMOS96 43a1p, GROMOS96 53a6, CHARMM27, and OPLS-AA/L force fields. The effects of charge-groups, terminal capping, and phosphorylation on the peptide folding were also examined. Despite using identical starting structures and simulation parameters, we observed clear differences among the various force fields and even between replicates using the same force field. Our simulations show that the uncapped peptide folds into a native-like β-hairpin structure at 310 K when Amber ff99SB-ILDN, Amber ff99SB*-ILDN, Amber ff99SB, Amber ff99SB*, Amber ff03, Amber ff03*, GROMOS96 43a1p, or GROMOS96 53a6 were used. The CHARMM27 simulations were able to form native hairpins in some of the elevated temperature simulations, while the OPLS-AA/L simulations did not yield native hairpin structures at any temperatures tested. Simulations that used charge-groups or peptide capping groups were not largely different from their uncapped counterparts with single atom charge-groups. On the other hand, phosphorylation of the threonine residue located at the β-turn significantly affected the hairpin formation. To our knowledge, this is the first study comparing such a large set of force fields with respect to β-hairpin folding. Such a comprehensive comparison will offer useful guidance to others conducting similar types of simulations.
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影响因子：
5.5
作者：
Beauchamp, Kyle A.;Lin, Yu-Shan;Das, Rhiju;Pande, Vijay S.
通讯作者：
Pande, Vijay S.
影响因子：
2.9
作者：
Best, Robert B.;Mittal, Jeetain
通讯作者：
Mittal, Jeetain
DOI：
10.1080/07391102.2011.10507403
发表时间：
2011-12-01
影响因子：
4.4
作者：
Cao, Zanxia;Liu, Lei;Wang, Jihua
通讯作者：
Wang, Jihua
DOI：
10.1074/jbc.m111.316471
发表时间：
2012-02-24
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Camp ND;James RG;Dawson DW;Yan F;Davison JM;Houck SA;Tang X;Zheng N;Major MB;Moon RT
通讯作者：
Moon RT
影响因子：
4.4
作者：
Fukunishi, H;Watanabe, O;Takada, S
通讯作者：
Takada, S