计算方法
计算模拟对于生物化学过程的描述是必不可少的，它可以在反应机理的分子水平上给出细节信息。例如，模拟这些过程的动力学，从而揭示了它们发生的时间尺度的信息。计算模拟主要研究，在不同的系统中，发生在从飞秒(超快)到微秒(慢)的时间尺度内物理-化学过程。
计算的方法包括：
随系统时间演化的动态方法。在超快过程的模拟中将引入表面跳越(Surface Hopping)和多重生成(Multiple Spawning)方法；对于较慢过程的描述，将采用自动反应机理搜索方法、经典分子动力学和增强采样方法。
量子力学/分子力学(QM/MM)多层划分方案，对大分子的关键部位（QM区间）的电子性质计算以及其他部分（MM区间）的动力学性质对关键部位的影响（通过结合分子动力学模拟实现）。全原子模拟和粗粒化分子模拟可用于描述MM区间。
方法的发展：在整个动力学过程中对系统电子结构进行定量表征，以获得物理化学性质。
研究的体系
90%的癌症死亡的原因是转移，阻止和减缓癌细胞转移有望控制癌症，将其变为慢性病。然而，目前还没有很好的办法去做到。本课题组主要针对癌症相关蛋白/酶等开展一下研究：
1. 量子生物化学方面：
1）生物酶反应机制 (QM/MM、QM/MM/MD)
2）小分子与蛋白互作 （QM/MM方法）
2. 计算生物物理方面：
1)蛋白质结构动态与功能关系的研究（relationship between structural dynamics and function）
2) 药物小分子与蛋白质相互作用的理论研究 （ligand binding）
3) 蛋白-蛋白相互作用的研究 （protein-protein interaction）
4) 蛋白质折叠（protein folding）
5) 相分离（phase separation）
3. 计算方法使用：
QM：CC、CASSCF/CASPT2、DMRG、DFT
AAMD（全原子）：FEP、TI、metadynamics、umbrella sampling、etc.
CGMD（粗粒化）：martini、Siruh、HPS-SS、AICG2+、etc.
4. 机器学习
1) CC to DFT; DFT to semiempirical
2）QM to AA force field
3) AA to CG
4) ML potential for ligand binding in MD
metadynamics、umbrella sampling、FEP/TI 、etc.
6) hydrid QM/ML/MM/MD
方法：MD，QM，QM/MM，QM/MM/MD，coarse grained methods，AI-based methods
Molecular simulations are essential for the characterization of any chemical process, allowing the description the detaied informtion at the molecular level of the reaction mechanisms. For example, the dynamics of biological processes can be simulated to reveal the information about the time scales in which they occur. This can be even more clear and realistic than experimental study. For physical-chemical processes in different systems, the important evernts the take place in time scales ranging from femtoseconds (ultrafast) to microseconds (slow) can be studied.
Those biological processes can be tackled with different theoretical approaches:
1. TIme-dependent simulation: To follow the temporal evolution of the systems. Surface Hopping and Multiple
Spawning methods can be used for the simulation of ultrafast processes; while automatic reaction mechanism search
methods, MD simulation combined with enhanced sampling approaches can be used to describe slower processes.
2. Quantum mechanical/molecular mechanical (QM/MM) multilayer partitioning schemes can be used for the calculation
of the electronic properties of important region of molecule. all-atomic and coarse-grained MD simulation can be used
for the description of the remaining region.
3. Methods Development: To obtain properties of physical-chemical interest and quantitatively characterize the electronic
structure of the system throughout the dynamics process of the system
System
Metastasis accounts for more than 90 percent of cancer related deaths, yet effective therapeutics for metastatic cancer is lacking.
The research in our group (the computational biology) is to study protein-ligand and protein-protein interactions relating to cancer,
in particular actin interpalys with actin-binding proteins (ABPs). Also, how the small molecule affect the interaction between actin and
ABPs. Actin is a family of globular multi-functional proteins that form microfilaments.
Our group uses structure-based modeling to understand these biological processes, often in close collaboration with experimental groups.
Students' study in our group:
1. reaction mechanism of enzyme （QM/MM，QM/MM/MD）
2. relationship between structural dynamics and function -MD simulation（REMD，resp2，etc）
3. ligand binding --metadynamics，FEP，umbrella sampling， etc
4. protein folding --coarse grained MD
5. phase separation --coarse grained MD