Systematic validation of protein force fields against experimental data.
Systematic validation of protein force fields against experimental data.
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DOI：
10.1371/journal.pone.0032131
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shaw DE
中科院分区：
文献类型：
--
作者：
Lindorff-Larsen K;Maragakis P;Piana S;Eastwood MP;Dror RO;Shaw DE
分子动力学模拟为捕捉生物大分子的结构、运动和相互作用提供了一个完整的原子细节。然而，这种模拟的准确性严重依赖于力场——用于近似作用于模拟分子系统的原子级力的数学模型。在这里，我们基于实验数据与分子动力学模拟的比较，对八种不同的蛋白质力场进行了系统和广泛的评估，达到了以前无法达到的时间尺度。首先，通过与实验核磁共振数据的广泛比较，我们检查了力场描述折叠蛋白质结构和波动的能力。其次，我们通过比较小肽优先填充螺旋结构或片状结构的实验和模拟数据，量化了对不同二级结构类型的潜在偏差。第三，我们测试了力场折叠两个小蛋白质的能力，一个是α-螺旋结构，另一个是β-片状结构。结果表明，随着时间的推移，力场已经得到了改进，最近的版本虽然不完美，但提供了对蛋白质的许多结构和动力学特性的准确描述。
Molecular dynamics simulations provide a vehicle for capturing the structures, motions, and interactions of biological macromolecules in full atomic detail. The accuracy of such simulations, however, is critically dependent on the force field—the mathematical model used to approximate the atomic-level forces acting on the simulated molecular system. Here we present a systematic and extensive evaluation of eight different protein force fields based on comparisons of experimental data with molecular dynamics simulations that reach a previously inaccessible timescale. First, through extensive comparisons with experimental NMR data, we examined the force fields' abilities to describe the structure and fluctuations of folded proteins. Second, we quantified potential biases towards different secondary structure types by comparing experimental and simulation data for small peptides that preferentially populate either helical or sheet-like structures. Third, we tested the force fields' abilities to fold two small proteins—one α-helical, the other with β-sheet structure. The results suggest that force fields have improved over time, and that the most recent versions, while not perfect, provide an accurate description of many structural and dynamical properties of proteins.
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影响因子：
3.4
作者：
Best, Robert B.;Buchete, Nicolae-Viorel;Hummer, Gerhard
通讯作者：
Hummer, Gerhard
影响因子：
64.8
作者：
Lindorff-Larsen, K;Best, RB;Vendruscolo, M
通讯作者：
Vendruscolo, M
影响因子：
2.7
作者：
Lindorff-Larsen, K;Best, RB;Vendruscolo, M
通讯作者：
Vendruscolo, M
影响因子：
3
作者：
Duan, Y;Wu, C;Kollman, P
通讯作者：
Kollman, P
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML