报告人学术简介
  郭鸿教授在吉林大学师从唐傲庆先生研究密度矩阵理论，获硕士学位。在哈佛大学师从诺贝尔奖得主Martin Karplus教授，获博士学位。在哈佛学习期间，郭鸿采用从头算量子化学方法研究了蛋白质肽键的氢键作用，揭示出肽键的氢键相互作用具有高度的协同性，并在结构和能量方面产生一些重要影响；他和Martin Karplus提出有必要对大多数模拟中使用的经典力场进行修正，可用随外部扰动变化（例如：电荷极化效应）而调整内部参数的力场。其后加入加拿大院士Dennis Salahub教授的研究组，将以上氢键的极化效应推广到酶催化反应。1998年返回哈佛大学参与Martin Karplus教授及诺贝尔奖得主William Lipscomb的工作，揭示出与诱导契合模型不同，酶可能在催化反应中诱导底物发生构象变化，使底物结构沿反应坐标向过渡态方向改变，从而起到催化作用。2002年他进入美国田纳西大学，2013年获该校终身正教授。郭鸿教授长期专注于QM/MM分子动力学模拟，研究生物大分子体系中的催化反应机制，解释酶催化及底物/产物特异性的基本原理。近年来，郭鸿等人提出了一种新的酶催化反应机制，即酶具有保持反应构象的能力，在反应过程中防止其过早发生构象扭曲成为低活性形式；还提出，由PTM（蛋白质翻译后修饰）诱导的底物辅助激活 (Substrate-Assisted Stimulation) 是实现PTM写入及调控PTM交互作用的潜在内在机制之一。
报告内容
  There are four lectures. The first two lectures provide some important background information for studying proteins (enzymes). We will first discuss some textbook examples of protein structure and function that demonstrate the importance of proteins and their functions in biology and human health (lecture 1). The methods of analyzing enzyme kinetic data and determining enzyme catalytic efficiency will be discussed next (Lecture 2). One of the important tasks in biochemistry is to understand what strategies that natural enzymes use to enhance the rates of reactions. Such knowledge is of fundamental importance for designing highly active enzymes with efficiencies that rival the rate enhancements of natural enzymes. In lecture 3, we demonstrate that enzymes might have evolved to have the ability to preserve reactive conformations during enzyme-catalyzed reactions using QM/MM computational methods, an important mechanism that, to the best of our knowledge, has not been recognized previously. In Lecture 4, we will discuss how pre-installed histone post-translational modifications (PTMs) can affect activity and specificity of histone modifying enzymes and explore general mechanisms governing their crosstalk. We will discuss our recently proposed hypothesis that PTM-induced substrate-assisted stimulation may be one of the potential underlying mechanisms for writing PTM and controlling PTM crosstalk.