郭鸿 Professor, Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee and UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory

本次报告将介绍最近关于不同计算方法在蛋白质研究中的一些应用。

我们将首先展示基于量子力学/分子力学并用的分子动力学模拟，以了解酶的催化机制和底物特异性，包括：

（1）特异地基于单甲基化H4K20底物（H4K20me1）产生二甲基化产物（H4K20me2）的独特Suv4-20家族蛋白赖氨酸甲基转移酶（PKMT）（JCTC，2017 ）; 

（2）其他一些PKMTs的底物特异性探索（Scientific Report，2017）; 

（3）RING E3-E2〜nedd8靶标复合物中的泛素样NEDD8转移（JCIM，2018）; 

（4）(4S)-柠檬烯合酶催化的(3S)-芳樟酰基二磷酸酯（LPP）的(4S)-α-萜品基阳离子的生物合成（Molecules：Free Issue in Free Energy Simulations，2018）。

其次，我们将讨论如何使用蛋白质结构预测方法来了解植物中重要酶的某些特征及其功能（Nature Communication，2017）。

此外，我们将展示一种用于从蛋白质组和不同蛋白质组合中鉴定，解释和提取生物学规律的新方法（Int. J. Genomics，2018）。

In my talk, we will discuss some of our recent work on the applications of different computational approaches to study proteins. We will first show the results of molecular dynamic (MD) simulations with QM/MM potentials in understanding the catalytic mechanisms and substrate specificity of enzymes (in collaboration with experimentalists in some cases). The enzymes to be discussed include: (1) An unique Suv4-20 family of protein lysine methyltransferases (PKMTs) that generate di-methylated product (H4K20me2) based exclusively on the mono-methylated H4K20 substrate (H4K20me1) (published in JCTC, 2017); (2) Substrate specificity exploration of some other PKMTs (Scientific Report, 2017); (3) Ubiquitin-like NEDD8 transfer in RING E3-E2~nedd8-target Complex (JCIM, 2018); (4) biosynthesis of the (4S)-α-terpinyl cation from (3S)-linalyl diphosphate (LPP) catalyzed by (4S)-limonene synthase (Molecules: Special Issue in Free Energy Simulations, 2018). In addition, we will discuss how to use the method of protein structure prediction to understand some feature of important enzymes in plants and their function (Nature Communication, 2017). Furthermore, we will show a new approach for identification, interpretation and extraction of biological insights from proteomes and different protein sets (Int. J. Genomics, 2018).