Validation challenge of density-functional theory for peptides-example of Ac-Phe-Ala5-LysH(+).
Validation challenge of density-functional theory for peptides-example of Ac-Phe-Ala5-LysH(+).
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DOI：
10.1021/jp412055r
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发表时间：
2014-03
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影响因子：
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通讯作者：
M. Rossi;S. Chutia;M. Scheffler;V. Blum
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作者：
M. Rossi;S. Chutia;M. Scheffler;V. Blum
我们评估了一组用于预测肽链二级结构的交换相关泛函的性能，直到一个新的多体弥散校正杂交密度泛函，被其原作者称为PBE0+MBD*。为了验证，我们首先比较了73个小三残基肽构象的已发表的高水平基准构象能级（单、双和扰动三重能级的偶联簇，CCSD(T)），确定范德华校正的PBE0函数产生的平均误差仅为~ 20 meV （~ 0.5 kcal/mol）。这与非色散校正PBE0的~ 40-50 meV和不同经验力场的40-100 meV（估计为丙氨酸四肽）相比。对于形成二级结构的较长的肽链，CCSD(T)水平的基准数据目前无法负担。因此，我们转向实验研究的ac - ph - ala5 - lysh（+）肽，通过红外光谱确定了四个紧密竞争的构象。相比之下，一个详尽的理论构象空间探索产生了至少11个相互竞争的低能极小值。我们发现(i)需要多体色散校正，（ii） PBE0+MBD*的杂化功能性质，以及（iii）零点校正来揭示实验观察到的四种结构在低温下将被填充的最小值。
We assess the performance of a group of exchange-correlation functionals for predicting the secondary structure of peptide chains, up to a new many-body dispersion corrected hybrid density functional, dubbed PBE0+MBD* by its original authors. For the purpose of validation, we first compare to published, high-level benchmark conformational energy hierarchies (coupled cluster at the singles, doubles, and perturbative triples level, CCSD(T)) for 73 conformers of small three-residue peptides, establishing that the van der Waals corrected PBE0 functional yields an average error of only ∼20 meV (∼0.5 kcal/mol). This compares to ∼40-50 meV for nondispersion corrected PBE0 and 40-100 meV for different empirical force fields (estimated for the alanine tetrapeptide). For longer peptide chains that form a secondary structure, CCSD(T) level benchmark data are currently unaffordable. We thus turn to the experimentally well studied Ac-Phe-Ala5-LysH(+) peptide, for which four closely competing conformers were established by infrared spectroscopy. For comparison, an exhaustive theoretical conformational space exploration yields at least 11 competing low energy minima. We show that (i) the many-body dispersion correction, (ii) the hybrid functional nature of PBE0+MBD*, and (iii) zero-point corrections are needed to reveal the four experimentally observed structures as the minima that would be populated at low temperature.