1. 关于文献学习
发表时间：优先考虑近五年内发表的论文，这些文献通常包含最新的研究成果和趋势。尽管如此，某些领域可能存在经典论文，其影响力可能跨越数十年甚至百年，因此也应予以关注；
论文影响力：选择具有较高影响因子的期刊，如《Nature》、《Science》和《Cell》等，这些期刊的论文往往经过严格的同行评审，具有较高的学术价值。同时，不应忽视影响因子较低的期刊，它们同样可能包含有价值的研究和见解，可以先从影响因子低的论文着手，学习背景、思路、方法，思考还有哪些可以改进的地方；
关键词选择：在进行文献搜索时，应使用与研究领域紧密相关的关键词，如“peptide pesticide” +“molecular dynamics” + “machine learning”等，以提高搜索的准确性和相关性；
搜索引擎：推荐使用Google Scholar进行文献搜索，该平台覆盖广泛的学术资源，是获取专业文献的有效途径；
2. 多肽相关介绍
自组装多肽
自组装多肽介绍：
- 超分子多肽自组装在生物医学中的应用 (ijournals.cn)
- Computational Design of Peptide Assemblies | Journal of Chemical Theory and Computation (acs.org)
自组装多肽相关科研进展：
- 西湖大学利用 Transformer 分析百亿多肽的自组装特性，破解自组装法则
- 深研院化生学院韩伟/李子刚研究团队在多肽自组装设计和机理研究领域取得重要进展 (pku.edu.cn)
- 博导王怀民与他的“功能分子材料”战丨Lab Show (westlake.edu.cn)
-【亮点服务】西湖大学理学院王怀民团队最新成果登上Nano Letters封面丨控制多肽组装动力学，在细胞内引起“蝴蝶效应”-西湖大学 物质科学公共实验平台 (westlake.edu.cn)
- 天然短肽水凝胶研发新平台丨Nature Communications 刊发王怀民实验室最新研究成果 (westlake.edu.cn)
- 南开团队实现多肽原位自组装赋能癌细胞膜功能化修饰-南开要闻-南开大学 (nankai.edu.cn)
- 王浩课题组在“体内自组装”多肽药物领域取得系列新进展----国家纳米科学中心 (cas.cn)
- Computationally designed peptides for self-assembly of nanostructured lattices | Science Advances
3. 分子模拟软件与分子力场
经典分子动力学GROMACS: GROMACS Tutorials (mdtutorials.com)
第一性原理分子动力学VASP: Category:Molecular dynamics - VASP Wiki
粗粒化分子动力学力场Martini: Home (cgmartini.nl)
全原子分子动力学力场Charmm: MacKerell Lab (umaryland.edu)
4. MD模拟运行
Step 1: Software installation
Software 1 - PuTTY: Install PuTTY, a free and open-source terminal emulator, which facilitates secure remote connections to a supercomputer. You can download it from the official website. Download PuTTY
Software 2 - WinSCP: Install WinSCP, a secure file transfer client for Windows environments that integrates with the supercomputer's file system. It can be downloaded from the provided link. Download WinSCP
Software 3 - PyMOL: Install PyMOL, a molecular visualization software used for creating and analyzing the structure of peptides and proteins, as well as visualizing simulation results. It is available for download at the official site. Download PyMOL.
Additional notes
Note 1 - PuTTY: Utilize PuTTY as the primary interface for command-line interactions with the supercomputer. On macOS, the built-in "Terminal" application can be used as an alternative. To initiate a session, execute the command ssh -p 22 username@login.hpc.xjtlu.edu.cn, followed by entering your password.
Note 2 - WinSCP: This tool is exclusively for Windows users and allows for the editing and management of files on the XJTLU supercomputer. macOS users may need to utilize the command-line editor vim within the Linux terminal for file manipulation.
Note 3 - PyMOL: PyMOL is essential for generating and visualizing the structural data of biological molecules such as peptides and proteins, providing insights into the dynamics of simulations.
Executions you need to perform
Execution 1 - Session Configuration in PuTTY: Launch PuTTY and configure the session by entering the Host Name and Port number (Port: 22) (Figure 1 left). You may save this session with a personalized name in the "Saved Sessions" field and then click "Save" to store your settings. Subsequently, click "Open" to initiate the session (Figure 1 right), which will present a terminal window. Enter your password to authenticate and gain access.
Figure 1: Putty configuration and login interface
Execution 2 - File Transfer and Management with WinSCP: Launch WinSCP (Figure2 left) and initiate a connection by entering the required credentials: the host name login.hpc.xjtlu.edu.cn, the port number 22, your designated username, and password. Once you have entered these details, select the option to save your session for future convenience and then proceed to log in. Upon successful authentication, you will be presented with the WinSCP interface (Figure 2 right), which features two panels: the left panel represents your local file system (in red box), typically accessible from your desktop or laptop, while the right panel (in yellow box) displays the remote file system of the supercomputer. To create a new directory on the supercomputer folder, utilize the command-line interface provided by PuTTY. Enter the command mkdir anyfoldername within the terminal. This action will generate a new directory named anyfoldername under the path /gpfs/work/pha/Username on the supercomputer's file system.
By adhering to Step 1, you can efficiently manage and transfer files between your local machine and the supercomputer, streamlining your research workflow.
Figure 2: Winscp configuration and login interface
Following the initial preparations (i.e., step 1) for MD simulation execution, the subsequent steps (step 2-4) involves meticulously preparing the input files for the simulations, running the simulations and postprocessing the results. Specifically, we will use the example of the secondary structure evolution of short peptides in aqueous environment for setting up an MD simulation. This example will employ an all-atom MD simulation approach, utilizing the CHARMM force field for accurate biomolecular interaction representation and the GROMACS simulation package for robust computational processing.
Step 2: Preprocessing: preparation of input files
Preparation 1 - PDB file (peptide structure file): To initiate MD simulations for peptides, a structural file in PDB format is essential. The PDB format, acronym of Protein Data Bank, is the standard for representing the three-dimensional structures of peptides and proteins. Utilizing PyMOL, you can generate the required PDB file as follows:
1- Launch PyMOL, please skip the activation process if a license is not available by selecting "skip the activation".
2-Access the compressed folder containing the downloaded files from Alphafold3, decompress it, and then import a structural file, such as "fold_419_model_1.cif," into PyMOL. The structure will be displayed, as indicated in the provided illustration (Figure 3 left).
3-Proceed to "File - Export Molecule," select the "Save" option, and choose "PDB" as the file type for export (Figure 3 right). Name the exported file "test.pdb" (or any other name you want) for usage in subsequent step (Step 2).
Figure 3: Pymol configuration and saving interface
Preparation 2 - Additional simulation files: To set up your MD simulation environment, perform the following actions:
1-Create a Directory: Open the PUTTY terminal and navigate to the base directory "/gpfs/work/pha/Username". Create a new directory named "Username-20240723-test1" or another name of your choosing. You can create this directory using Winscp by right-clicking and selecting "新建-目录" (New-Directory), or by using the command "mkdir Username-20240723-test1" in the PUTTY terminal.
2-File Upload: Transfer the following files to the "Username-20240723-test1" directory: "test.pdb", "submitcpu.sh", "submitgpu.sh", "control.sh", "ions.mdp", "enmin.mdp", "nvt.mdp", "npt.mdp", "prod.mdp", "spc216.gro", "peptide.top"and the "Charmm36-jul2022.ff" folder (This folder contains the Charmm force field).
3-File processing: In the PUTTY terminal, execute "dos2unix *" to convert file formats from Windows to Linux. Then, run "chmod +x *.sh" to grant execute permissions to all shell script files. Before executing the above commands, ensure you are in the correct directory by using "cd Username-20240723-test1".
Addtional explanations and annotations of each files are included inside the files.
Step 3: Running the MD simulations
In your Putty terminal, execute sbatch submitcpu.sh to submit to CPUs (26 cpu cores are available) or sbatch submitgpu.sh to submit to GPUs (4 GPU cards are available). You simulations should be able to run!
There are totally eight steps of the MD simulations as in the control.sh file, and the generated boxes of each step are illustrated in Figure 4.
S1: Build a water box --> water_box.gro
S2: Do energy minimization of water box --> water_min.gro
S3: Insert the peptide to the energy-minimized water box --> test_water.gro
S4: Add ions to neutralize the chage --> test_water_ion.gro
S5: Do energy minimization of water and peptide --> test_chx_water_min.gro
S6: Do equilibration at NVT of water and peptide --> test_chx_water_NVT.gro
S7: Do equilibration at NPT of water and peptide --> test_chx_water_NPT.gro
S8: Do production of water and peptide --> test_chx_water_prod.gro (This is your final results of the MD simulation of peptide secondary structure)
Figure 4: Simulation box generated at the end of each step
Step 4: Post-processing and visualizations
Examples
Note: Files are available upon reasonable requests by emailing to benwang@hku.hk
GROMACS-MARTINI force field粗粒化模拟
- 多肽自组装模拟
GROMACS-CHARMM force field全原子模拟
- 多肽与蛋白结合动力学模拟
