Department of Chemistry and NIS (Nanostructured Interfaces and Surfaces) Center, University of Torino , Via P. Giuria 7, 10125 Turin, Italy.
J Chem Theory Comput. 2017 Jan 10;13(1):370-379. doi: 10.1021/acs.jctc.6b01045. Epub 2016 Dec 15.
We studied the sensitivity of the energetic and geometrical features of the proline ring (pyrrolidine) to the quantum mechanical computational approach by adopting the proline monomer, trimer, and polymer, as simplified collagen protein models. Within the Density Functional Theory (DFT) approach, we tested the ability of different functionals (GGA PBE and the hybrid B3LYP), added with a posteriori empirical dispersion corrections (D), to predict the conformational potential energy surface of the five-membered heterocycle pyrrolidine ring for the above models, dictating the collagen main features. We also compared the DFT-D results with those from the recently proposed cost-effective HF-3c method and our variant HF-3c-027, both based on Hartree-Fock Hamiltonian and Gaussian minimal basis set properly corrected for basis set superposition error, structure deficiencies, and dispersion interactions. We found that dispersion interactions are essential to destabilize specific conformers. While the HF-3c and its HF-3c-027 variant are unreliable to predict accurately the energy of the ring conformers, structures are accurate. Indeed, the cost-effective DFT-D//HF-3c-027 approach in which the energetic is from the accurate DFT-D method on HF-3c-027 structures provides energetic in line with that derived by the costly DFT-D//DFT-D approach, paving the way to simulate more realistic collagen models of much larger size. The adoption of either PBE or B3LYP functional for the electronic part of the DFT-D method gives very similar results, recommending the first as the most cost-effective method for simulating large collagen models. The predicted most stable conformation computed for the periodic poly proline (type II) model allows for a higher flexibility, in agreement with experimental studies on collagen protein. The present results open the way to large-scale calculations of the collagen/hydroxyapatite system, crucial for understanding the atomistic details in bones and teeth.
我们采用脯氨酸单体、三聚体和聚合物作为简化的胶原蛋白模型，研究了脯氨酸环（吡咯烷）的能量和几何特征对量子力学计算方法的敏感性。在密度泛函理论（DFT）方法中，我们测试了不同泛函（GGA PBE 和混合 B3LYP）的能力，外加后验经验色散校正（D），以预测上述模型中五元杂环吡咯烷环的构象势能表面，决定胶原蛋白的主要特征。我们还将 DFT-D 的结果与最近提出的经济高效 HF-3c 方法和我们的 HF-3c-027 变体进行了比较，这两种方法都是基于 Hartree-Fock 哈密顿量和适当修正了基组超交误差、结构缺陷和色散相互作用的高斯最小基组。我们发现色散相互作用对于使特定构象不稳定是必不可少的。虽然 HF-3c 及其 HF-3c-027 变体对于准确预测环构象的能量是不可靠的，但结构是准确的。实际上，经济高效的 DFT-D//HF-3c-027 方法，其中能量来自 HF-3c-027 结构上的准确 DFT-D 方法，提供了与昂贵的 DFT-D//DFT-D 方法得出的能量相吻合的能量，为模拟更大尺寸的更真实的胶原蛋白模型铺平了道路。DFT-D 方法的电子部分采用 PBE 或 B3LYP 泛函会得到非常相似的结果，建议采用第一种方法作为模拟大型胶原蛋白模型的最具成本效益的方法。对于周期性聚脯氨酸（II 型）模型计算出的最稳定构象允许更高的灵活性，这与胶原蛋白的实验研究一致。目前的结果为胶原/羟基磷灰石系统的大规模计算开辟了道路，这对于理解骨骼和牙齿中的原子细节至关重要。
