Katagiri Daisuke, Fuji Hideyoshi, Neya Saburo, Hoshino Tyuji
Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
J Comput Chem. 2008 Sep;29(12):1930-44. doi: 10.1002/jcc.20963.
Molecular dynamics (MD) simulations are extensively used in the study of the structures and functions of proteins. Ab initio protein structure prediction is one of the most important subjects in computational biology, and many trials have been performed using MD simulation so far. Since the results of MD simulations largely depend on the force field, reliable force field parameters are indispensable for the success of MD simulation. In this work, we have modified atom charges in a standard force field on the basis of water-phase quantum chemical calculations. The modified force field turned out appropriate for ab initio protein structure prediction by the MD simulation with the generalized Born method. Detailed analysis was performed in terms of the conformational stability of amino acid residues, the stability of secondary structure of proteins, and the accuracy for prediction of protein tertiary structure, comparing the modified force field with a standard one. The energy balance between alpha-helix and beta-sheet structures was significantly improved by the modification of charge parameters.
分子动力学（MD）模拟在蛋白质结构与功能研究中得到广泛应用。从头算蛋白质结构预测是计算生物学中最重要的课题之一，到目前为止已经进行了许多使用MD模拟的尝试。由于MD模拟的结果在很大程度上取决于力场，可靠的力场参数对于MD模拟的成功不可或缺。在这项工作中，我们基于水相量子化学计算对标准力场中的原子电荷进行了修改。结果表明，通过广义玻恩方法进行MD模拟，修改后的力场适用于从头算蛋白质结构预测。将修改后的力场与标准力场进行比较，从氨基酸残基的构象稳定性、蛋白质二级结构的稳定性以及蛋白质三级结构预测的准确性等方面进行了详细分析。通过修改电荷参数，α-螺旋和β-折叠结构之间的能量平衡得到了显著改善。
