Toward a Coarse-Grained Protein Model Coupled with a Coarse-Grained Solvent Model: Solvation Free Energies of Amino Acid Side Chains
Toward a Coarse-Grained Protein Model Coupled with a Coarse-Grained Solvent Model: Solvation Free Energies of Amino Acid Side Chains
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DOI：
10.1021/ct800184c
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发表时间：
2008-11-01
影响因子：
5.5
通讯作者：
Wu, Yun-Dong
中科院分区：
文献类型：
--
作者：
Han, Wei;Wan, Cheuk-Kin;Wu, Yun-Dong
最近，我们报道了使用粗粒(CG)肽模型和CG水模型的分子动力学(MD)模拟能够以103倍的正常速度再现带有非极性侧链的短肽的许多结构和热力学特征(JCTC，2007，3,2146-2161)。为了进一步开发用于MD模拟的CG蛋白质模型，我们系统地将所有20种自然出现的氨基酸的侧链参数化。我们通过对13个小分子的二面体势、8个有机分子的液体密度和自溶剂化自由能以及35个有机小分子的水合自由能进行拟合，得到了这些参数。在包括烷烃、醇、醚、酮/醛、胺、酰胺、芳烃、羧酸、硫化物/硫醇、烷基胺和羧酸根离子在内的11类化合物中，计算的水合自由能与实验值的平均误差约为1.4kJ/mol。19个氨基酸侧链类似物从环己烷到水的转移自由能计算的平均误差约为2.2kJ/mol。这些结果与全原子模型的结果相当。
Recently, we reported that molecular dynamics (MD) simulations using a coarse-grained (CG) peptide model coupled with a CG water model are able to reproduce many of the structural and thermodynamic features of short peptides with nonpolar side chains at 103 times the normal speed (JCTC, 2007, 3, 2146-2161). To further develop a CG protein model for MD simulations, we systematically parametrized the side chains of all 20 naturally occurring amino acids. We developed the parameters by fitting the dihedral potentials of 13 small molecules, the densities and self-solvation free energies of liquids of eight organic molecules, and the hydration free energies of 35 small organic molecules. In a set of 11 classes of compounds (105 in total) including alkanes, alcohols, ethers, ketones/aldehydes, amines, amides, aromatics, carboxylic acids, sulfides/thiols, alkyl ammoniums, and carboxylate ions, the average error in the calculated hydration free energies compared with experimental results is about 1.4 kJ/mol. The average error in the calculated transfer free energies of the 19 side-chain analogues of amino acids from cyclohexane to water is about 2.2 kJ/mol. These results are comparable to the results of all-atom models.