中文摘要：

蛋白激酶通过磷酸化蛋白底物来调节细胞内的信号转导途径，是重要的药物设计靶标。蛋白激酶A（PKA）是最早获得催化结构域X射线衍射晶体结构的激酶，是蛋白激酶家族中代表性结构。本文综述了PKA在计算化学领域的研究进展，包括PKA全酶及其催化（C）亚基和调节（R）亚基在水溶液中的分子动力学模拟研究，磷酰基转移机理和C亚基与其抑制剂balanol的结合自由能预测、柔性对接。分子动力学、分子对接、同源模建、QM／MM等计算机辅助设计方法在该体系中得到运用。

英文摘要：

Protein kinases regulate the signal transduction pathways in cell by phosphorylating the protein kinase substrate, and they are important targets in drug design. Protein kinase A （PKA） is the first kinase that was obtained X-ray structure of its catalytic domain, and is regarded as prototype for protein kinase superfamily. The progress in computational chemistry study of protein kinase A has been reviewed, including the molecular dynamics simulation study of PKA holoenzyme and its C subunit and R subunit in aqueous solution, phosphoryl transfer mechanism, the binding free energy predicting and flexible docking of C subunit with its inhibitor balanol. Various computational approaches are applied to this system, including molecular dynamics simulation, dock, homology modeling, QM/MM.