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标题: 网上公开的自由能/增强采样计算教程整理及主观简评 [打印本页]

作者
Author: student0618 时间: 2025-10-7 06:19
标题: 网上公开的自由能/增强采样计算教程整理及主观简评
本帖最后由 student0618 于 2025-11-19 17:17 编辑

(Working on English-to-Chinese translation slowly when I have time)

网上公开的自由能/增强采样计算教程整理及主观简评 (2025年10月)

List of Freely Accessible Tutorials on Free Energy / Enhanced Sampling Methods with Personal, Subjective Comments (October 2025)

目录 Table of contents

0. 前言 | Preface

0.1. 总评

0.2. 列表格式 | Format of each entry

0.3. 教程选择方向

1. 比较重要的简写 | List of abbrevations

2. 中文教程
2.1 计算化学公社帖文
2.1.1. Colvars (+NAMD)
2.1.2. Gromacs
2.2. 论坛上相关工具及脚本

3. 英文教程
3.1. Gromacs
3.1.1. 粗粒化马丁尼力场 | Coarse-Grained Martini forcefield
3.1.2. 全原子/联合原子力场 | All-atom/United atom forcefield

3.2. Amber
3.2.1. Amber官网教程 | Official Amber tutorials
3.2.2. GaMD-based methods
3.2.3. Grid Inhomogeneous Solvation Theory (GIST)
3.2.4. QM/MM umbrella sampling

3.3. Plumed
3.3.1. Basic
3.3.2. Metadynamics
3.3.3. 伞型采样 | Umbrella sampling
3.3.4. Replica Exchange
3.3.5. Special CV
3.3.6. Others

3.4. NAMD
3.4.1. NAMD 官网教程 | Official NAMD tutorials
3.4.2. LiveCoMS上发表的 NAMD教程 | NAMD Tutorials published on LiveCoMS

3.5. GROMOS

3.6. OpenMM

3.7. WESTPA

4. 相关网址或工具 | Related websites or tools

5. 结语 | Conclusion

0. 前言 Preface

相比起基本的MD 分子模拟，涉及增强采样/自由能计算的任务更爲复杂。最近因为要用到不同的自由能计算方法，更新及整理了以前存下来各主流MD程序的自由能计算教程连结。在此分享这自用的列表，对部分教程也加上自己从学生的角度看、完全主观的简评、以及一些使用上的备注，以供参考。

0.1. 总评 (个人主观意见)

网上公开免费的教程良莠不齐。论完整度、学习难度、论实作与基本理论的平衡: 个人认为特定基于CV增强采样方法教程比较大部分基于炼金术 (alchemical/alchemistry) 的教程优质、更清晰、更易理解。尤其是gromacs的FEP教程还是找不到理想的，挺可惜的。

很多LiveCoMS的教程比官网优质，但不保证如期刊的愿景会与时并进，因此要注意对应的程序版本。自创刊开始follow的我目前只看到WESTPA 和 GROMOS (不是GROMACS) 的教程有从V1.0更新至V2.0。

也吐槽一下Plumed的fill-in-the-blank输入文件填空题教程，到底是谁的主意？部分甚至没给答案？！这其实很妨碍学习的，对需要自学的人很不友善。

(顺带一提，个人认为最优秀的网上免费公开英文教程是Multiwfn手册及解晶体结构软件phenix的教程，至少目前看了多年的大小免费MD教程都无法达到那程度。)

0.2 列表格式 | Format of each entry

教程标题 Tutorial title

关键词 Keywords: Ctrl-F用的关键词
连结 Link: 教程的连结
简评/备注 Comments/Remarks: 完全主观的简评+备注, 从学生角度看对教程, 完整度、难度等的分析 (不包含语言上的难度)。用过的会较详尽，没用过的通常只粗略看一遍写一点注意事项或感想。

0.3. 教程选择方向

有些教程是多年前刚开始学习分子模拟时用过的，不保证和最新版本软件相容。部分教程只看过内容没实际跑过。
英文教程来源先找软件官网、方法/工具开发者的网站、其他主要是在Living Journal of Computational Molecular Science (LiveCoMS)发表的。
明白对不少论坛的读者来说较偏好中文视频教程。无奈我听不懂很多专有名词的发音，要盯着文字资料重复听才能明白；暂没有能力判断中文教程上的用词是否正确，因此不会列出任何本论坛以外的中文教程。也不会列出视频教程，因个人学习上偏好最好可以ctrl-f 的文字版或印出来放实体书签的资料，而这帖本来就是自用的合集。
不包括基本MD及MM/PB(GB)SA。
不讨论原理、不讨论什么时候用哪方法，需要的请查阅相关文献。
不包括过分依赖第三方Library、直接用python interface、以致几乎不会接触到背后MD程序输入文件的教程。
大部分帖文内容是先用英文写好再翻译为中文的(进度缓慢)，如有翻译错误请不吝赐正。一些专有名词为免出错就不翻译了。
尽量找了大部分主流程序的教程，但无法会包括所有的。

1. 比较重要的简写 | List of abbrevations

伞型采样 Umbrella Sampling (US)
Collective variables (CV)
Metadynamics (MetaD)
Well-tempered Metadynamics (WTM)
Adaptive Biasing Force (ABF)
Extended Adaptive Biasing Force (eABF)
Replica Exchange Molecular Dynamics (REMD)
Hamiltonian Replica Exchange (HREX) / Hamiltonian Replica Exchange Molecular Dynamics (HREMD/H-REMD)
Free Energy Perturbation (FEP)
Thermodynamic Integration (TI)
Gaussian accelerated molecular dynamics (GaMD)
accelerated weight histogram method (AWH)
Grid Inhomogeneous Solvation Theory (GIST)
Adaptively Biased Molecular Dynamics (ABMD), well-tempered ABMD (WT-ABMD), driven ABMD (D-ABMD)
Steered Molecular Dynamics (SMD)
Swarms-of-Trajectories String Method (STSM)
Weighted Ensemble (WE)
Absolute Binding Free Energy (ABFE)
Relative Binding Free Energy (RBFE)
Potentials of Mean Force (PMF)
Replica Exchange Umbrella Sampling (REMD-US / REUS)
On-the-fly Probability Enhanced Sampling (OPES)
Hamiltonian scaling in Replica Exchange with Solute Tempering (REST / REST1 /REST2 )

2. 中文教程

2.1 计算化学公社帖文
2.1.1. Colvars (+NAMD)

NAMD自由能计算教程—1、用eABF和WTM-eABF进行多维自由能计算 (出处: 计算化学公社)

关键词 Keywords: eABF, WTM-eABF, 多维自由能, Colvars

连结 Link: link
简评/备注 Comments/Remarks: colvars输入文件的解说也适用于gromacs-colvars联用的增强采样任务。大致上很清晰、详尽。

NAMD自由能计算教程—2、用WTM-λABF进行炼金术自由能计算 (出处: 计算化学公社)

关键词 Keywords: WTM-λABF, 炼金术 (alchemical, alchemistry), NAMD, Colvars

连结 Link: link
简评/备注 Comments/Remarks: NAMD适用。

2.1.2. Gromacs

GROMACS-2025.0原生PLUMED和Colvars对比

关键词 Keywords: meta-eABF(Colvars), WT-metaD(PLUMED), gromacs 2025.0/2025.1
连结 Link: link
简评/备注 Comments/Remarks: (1)这教程比较了原生gmx-plumed接口、gmx-colvars、及Plumed patch gromacs的 performance。(2) Colvars用法请参阅2.1.1教程及第4节连结的gromacs-colvars 手册。

GROMACS中伞型采样算法应用详解

关键词 Keywords: US, 分子穿膜, pull code, PMF
连结 Link: link
简评/备注 Comments/Remarks: 伞形采样教程，比较了不同pulling options的用法。

(very old, not recommended. Use official Plumed tutorials in section 3.3.4 instead!!! 老版本不建议使用，要用Plumed+gmx跑HREMD请参考3.3.4项列出的官方英文教程)

关键词 Keywords: HREMD (very old, not recommanded), gromacs 4.6.7
连结 Link: link
简评/备注 Comments/Remarks: Better use the official Plumed tutorials in section 3.3.4 instead!!!

2.2. 论坛上相关工具及脚本

AutoFEP

关键词 Keywords: FEP
连结 Link: post link git repo AutoFEP_For_GMX
简评/备注 Comments/Remarks: AutoFEP 工具的github 上有mdp应用模板

MUltidimensional Least Energy pathway (MULE)

关键词 Keywords: 势能面, Free energy surface (FES) 自由能面, 最低反应路径
连结 Link: link
简评/备注 Comments/Remarks: pathway finding on multidimensional free energy surface.

3. 英文教程
3.1. Gromacs

3.1.1 粗粒化马丁尼力场 Coarse-Grained Martini forcefield

Free energy techniques (Martini)

关键词 Keywords: Martini, 粗粒化 Coarse-Grained (CG), Free sampling, US, TI, partition coefficient, PMF, solvation free energy, GROMACS
连结 Link: link
简评/备注 Comments/Remarks: 作爲介绍自由能计算/增强采样理论的教程意外地写得很不错，甚至比很多全原子力场的教程优秀。它用同一个体系比较了三个不同采样方法(free sampling、伞型采样、FEP)如何计算一个粗粒化珠子在水相和有机溶剂中的溶解自由能。美中不足的是：(1) 用的是粗粒化力场，而大多要用这些方法的通常想用全原子力场。(2) 只用了一个珠子，实际应用(除了力场开发目的) 通常一个分子有多个珠子。(3) 没考虑如何处理带净电荷的体系 (4) 比起实作的教程，更偏向是用实例来阐述理论方法的教程。

3.1.2 全原子/联合原子力场 | All-atom/United atom forcefield

LiveCoMS tutorial
Molecular Dynamics: From Basics to Application

关键词 Keywords: US, FEP, PMF, solvation free energy, binding free energy, GROMACS
连结 Link: link github repo of the tutorial link
简评/备注 Comments/Remarks: 自由能部分(exercise 6及7) 很多内容是参考Justin Lemkul的教程。exercise 6 umbrella sampling, exercise 7 FEP (both inspired by Justin's tutorial). Pay attention to the gmx version it supports. My overall comments on this set of tutorials: see this link

GROMACS官网的资源及教程
Training resource and free online GROMACS tutorials
(网址 URL http://tutorials.gromacs.org)
(1) 这边我放文字版的连结，留意它同时有 Jupyter notebook 版可以直接在网上用binder跑。
(2) 个人对官网教程的评价：为了网上免下载用 binder跑教程，过多用python 将教程简单复杂化，反而比第三方用家写的更难学会。

Umbrella sampling (example: Binding free energy of binding of two pyrimidine molecules)

关键词 Keywords: US, GROMACS 2021 or later, PMF
连结 Link: link
简评/备注 Comments/Remarks: Simple system should be fast, still using commands in jupyter notebook can be confusing.

Solvation free energy of ethanol

关键词 Keywords: FEP, alchemical transformation, GROMACS 2023 (and 2022)
连结 Link: link
简评/备注 Comments/Remarks: Directly use vdw-q with fep-lambda, 7 lambda points. Using ethanol is, well, better than just methane at least... Still using bash commands in jupyter notebook can be confusing.

Potential of mean force using AWH method (example: DNA base pair opening)

关键词 Keywords: AWH, GROMACS 2022 (2021, 2020, 2019, 2018), multiple walkers, PMF
连结 Link: link
简评/备注 Comments/Remarks: Less common. Using bash commands in jupyter notebook can be confusing.

Solvation free energy of ethanol using AWH method

关键词 Keywords: AWH, GROMACS 2022
连结 Link: link
简评/备注 Comments/Remarks: Less common. Using bash commands in jupyter notebook can be confusing.

Justin Lemkul's tutorials

Tutorials at http://www.mdtutorials.com/gmx
(1) This is NOT the official GMX tutorial site
(2) see some disucssions here

Umbrella Sampling (Example: Binding of Amyloid Protofibrils)

关键词 Keywords: US, GROMACS 2018, PMF
连结 Link: link
简评/备注 Comments/Remarks: pure protein system, COM pull, accessary scripts may be confusing (scripts of the JPCB tutorial below are better)

Free Energy of van der Waals transformation
(Original title: Free Energy Calculations: Methane in Water)

关键词 Keywords: FEP, GROMACS 2018
连结 Link: link
简评/备注 Comments/Remarks: More theories, less practical. Simple methane solvation free energy calculation, only simplified topology and use vdw-lambda, 21 lambda states, hard to address practical problems that usually charges are important in solvation/binding. OPLS-AA forcefield.

Free Energy of Hydration

关键词 Keywords: FEP, GROMACS 2025.2
连结 Link: link
简评/备注 Comments/Remarks: More practical than the methane-in-water one, has example to transform both vdW and Electrostatic terms with 31 lambda states. CGenFF forcefield. Note: this tutorial use ethanol parameters provided with the forcefield and generate topology via pdb2gmx, if you work on your own molecule without that data in the forcefield pdb2gmx may not work. You will need to get the topology from e.g. the CGenFF server.

Tutorial published on JPCB
(1) See my previous comments on this set of tutorials here

Introductory Tutorials for Simulating Protein Dynamics with GROMACS (Example for US: chignolin β-Hairpin Unfolding)

关键词 Keywords: US, Gromacs 2024, PMF
连结 Link: https://doi.org/10.1021/acs.jpcb.4c04901
简评/备注 Comments/Remarks: scripts are now in python and much easier to use, pulling the small protein hairpin

Others
Alchemistry ABFE tutorial

关键词 Keywords: FEP, ABFE, TI, HREX, Gromacs 2016
连结 Link: link
简评/备注 Comments/Remarks: better and more complete than Justin's tutor, better than official tutor without unnecessary py, 20 lambda states (refer to literature or autofep for example mdp with fewer lambda)

PyAutoFEP

关键词 Keywords: FEP
连结 Link: toolkit github repo tutorial link
简评/备注 Comments/Remarks: lack explanations, support "GROMACS 2016 or newer, but 2022 and 2023 not yet supported", last updated 2 years ago

PMX
(1) All PMX Tutorials on http://pmx.mpibpc.mpg.de/tutorial.html
(2) Due to the major overlap in different workshop versions, I am only listing the latest workshops/examples here.

Solvation free energy

关键词 Keywords: alchemical , Solvation free energy, PMX
连结 Link: link
简评/备注 Comments/Remarks: generally complete but can explain more

Istanbul BioExcel EuroCC Workshop 2025 (Ligand Modification, RBFE)

关键词 Keywords: alchemical, RBFE, TI, Non-equilibrium free energy calculation
连结 Link: link
简评/备注 Comments/Remarks: generally complete but can explain more

Alchemical absolute protein–ligand binding free energies for drug design

关键词 Keywords: alchemical, ABFE, TI, Non-equilibrium free energy calculation
连结 Link: Paper link github repo link
简评/备注 Comments/Remarks: kinda fragmentated, not very organized. mainly input files and scripts for their paper. Example workfolw files in the PMX github repo: link

3.2. Amber
3.2.1. Official Amber tutorials at https://ambermd.org/tutorials/FreeEnergy.php

Thermodynamic Integration using soft core potentials (Example: benzene and phenol in lysozyme L99A)

关键词 Keywords: TI, alchemical, RBFE
连结 Link: link
简评/备注 Comments/Remarks: internal tool in Amber

Advanced Thermodynamic Integration Using ACES (Example: two inhibitors bound to the the human THr160-phospho CDK2/cyclin A protein)

关键词 Keywords: TI, FE-Workflow, Alchemical Enhanced Sampling (ACES), RBFE
连结 Link: link
简评/备注 Comments/Remarks: more complicated workflow, use additional FE-Workflow package

pKa Calculations using Thermodynamic Integration (Example: capped aspartate dipeptide)

关键词 Keywords: TI, pKa
连结 Link: link
简评/备注 Comments/Remarks: internal tool in Amber

Umbrella Sampling: A Potential of Mean Force in alanine dipeptide Phi/Psi Rotation (Example: alanine dipeptide torsion)

关键词 Keywords: US, PMF
连结 Link: link
简评/备注 Comments/Remarks: internal tool in Amber

Umbrella Sampling: Transferring methanol through a membrane

关键词 Keywords: US, membrane, PMF
连结 Link: link
简评/备注 Comments/Remarks: internal tool in Amber, pull to center and assume the FES of the two sides are equivalent due to symmetry

Free Energy Estimation for Conformers of Dialanine using EMIL

关键词 Keywords: TI
连结 Link: link
简评/备注 Comments/Remarks: internal tool in Amber, vacuum. have FAQ but not well-explained

Free energy calculations with the Free Energy Workflow Tool (FEW)

关键词 Keywords: TI, FEW
连结 Link: link TI section (link)
简评/备注 Comments/Remarks: This workflow has a prepartion section and 3 methods. TI is the 3rd tutorial, section 4.

Grid Inhomogeneous Solvation Theory for water thermodynamics: in Factor Xa

关键词 Keywords: GIST, free energy of solvation on 3D grid
连结 Link: link
简评/备注 Comments/Remarks: older version, some conficts with the recommandation of the new LiveCoMS tutorial.

Computing Binding Free Energy using the Attach-Pull-Release (APR) Method (Example: Host-guest system)

关键词 Keywords: attach-pull-release (APR)
连结 Link: link
简评/备注 Comments/Remarks: scripts in python, have hints on adapting the scripts on the user's own system.

The Nonequilibrium Free Energy (NFE) Toolkit for PMEMD AMBER: Capabilities, Examples, and Collective Variables

关键词 Keywords: ABMD, multiple-walker, WT-ABMD, H-REMD, T-REMD, SMD, US, STSM
连结 Link: link
简评/备注 Comments/Remarks: A list of methods with 3 examples of simple peptide torsion. All modules on sander, some ported to PMEMD.

3.2.2. GaMD-based methods
(1) only implemented in PMEMD not sander

GaMD-Amber: Tutorial

关键词 Keywords: GaMD, Amber, PyReweighting

连结 Link: example tutorial link manual link reweighting and free energy calculation link
简评/备注 Comments/Remarks: (1) Not very complete, need to use tutorial with manual. (2) For analysis, one may also refer to the NAMD-GaMD tutorial in section 3.4. (3) note the output freq required for accurate energy reweighting and diskspace: according to the README.md on PyReweighting's github, "Accurate energetic reweighting can be obtained from GaMD simulations of large biomolecular systems (e.g., with millions of atoms) using cumulant expansion to the 2nd order, provided that standard deviation of the boost potential is <= ~ 9 kcal/mol and a total of roughly 0.5 - 1 million frames are saved in the GaMD simulations.". In some cases, one may need to use MC to the 10th order reweighting, which is known to shift minima positions but can get the shape of the curves at least. (4) only full input example have been provided for GaMD, only fragmented inputs available for LiGaMD/LiGaMD2/pep-GaMD/PPI-GaMD.

3.2.3. Grid Inhomogeneous Solvation Theory (GIST)

Quantifying Spatially Resolved Hydration Thermodynamics Using Grid Inhomogeneous Solvation Theory [v1.0]

关键词 Keywords: GIST, free energy of solvation on 3D grid
连结 Link: LiveCoMS article link github repo link
简评/备注 Comments/Remarks: Newer than the official tutorial. (1) Don't sample too frequently, no more freqently than 2ps (2) For integrated quantities: 100ns traj. ; For mapping: 5-10ns traj,

3.2.4. QM/MM umbrella sampling

CCPBioSim QM/MM Workshop (QM/MM Modelling of Enzyme Reactions)

关键词 Keywords: US, QM/MM, Amber, Sander, PM6, PMF
连结 Link: https://github.com/CCPBioSim/qmmm-workshop
简评/备注 Comments/Remarks: Amber QM/MM to to model a chemical reaction in an enzyme (PM6 via sander). Input files on git repo, the tutorial itself is a Jupyter notebook.

3.3. Plumed
(1) Only list official tutorials, re-organized (version 2.9.x)
(2) Plumed can be used with many MD engines, including but not limited to Gromacs, Amber, NAMD, LAMMPS, OpenMM.
(3) Plumed tutorials are organized by workshop title/date, I try to reorganize them here based on types, and remove highly similar tutorials for clarity.
(4) Who on earth decided to make fill-in-the-blank tutorials?! Who?? Some even without providing the answer?
(5) Generally tutorials with "masterclass" are better and more updated than others, but I include older tutorials instead if the newer fill-in-the-blank tutorial does not provide answer.
(6) Other Plumed Tutorials not in the list may be found in the following website: https://www.plumed-tutorials.org/browse.html

3.3.1. Basic

PLUMED Masterclass 21.1: PLUMED syntax and analysis

关键词 Keywords: gromacs
连结 Link: link
简评/备注 Comments/Remarks: Trajectory analysis with plumed. A fill-in-the-blank tutorial, solution: link

PLUMED Masterclass 21.2: Statistical errors in MD

关键词 Keywords: free energy, histogram, block averages, bootstrap averages, Weighted averages, error estimation
连结 Link: link
简评/备注 Comments/Remarks: statistics and errors. While this one has answer, I think the script "merge-histograms.py" from the tutorial below is easier to use to get the error bars. Alternatively, for umbrella sampling one can always use Grossfield's wham for wham reweighting with error estimation.

(old tutorials) Trieste tutorial: Averaging, histograms and block analysis

关键词 Keywords: histogram, block averages, error estimation

连结 Link: link
简评/备注 Comments/Remarks: Error estimation with "merge-histograms.py" script. Refer to this discussion on how to get the errors for free energy with the script ("take delta-Hi (given by the third column in the merge-histograms.py output) and divide it by Hi (given by the second column in the merge-histograms.py output).")

Lugano tutorial: Using PLUMED with LAMMPS

关键词 Keywords: LAMMPS, phase separation
连结 Link: link
简评/备注 Comments/Remarks: For using plumed with LAMMPSanother fill-in-the-blank tutorial, solution: ".solutions" directory of the tarball link

3.3.2. Metadynamics

PLUMED Masterclass 21.4: Metadynamics

关键词 Keywords: MetaD, Gromacs, SMOG, CV
连结 Link: link
简评/备注 Comments/Remarks: Include some hints on how to choose a good CV. Fill-in-the-blanks tutorial with answer at link

PLUMED Masterclass 22.1: Funnel-Metadynamics

关键词 Keywords: MetaD, Funnel metadynamics, VMD
连结 Link: link files link
简评/备注 Comments/Remarks: (1) To use this method, enable funnel when you compile plumed. (2) additional tcl files for funnel setup and analysis in VMD: tooltip.tcl from this link and the FMAP plugins from this link. (3) this is an old tutorial with tpr files generated with gmx 5.1.4, can have many problems when running with newer gmx. Less headache if you use the tutorial but setup gmx inputs yourself. (4) the actual manual of funnel metadynamics is their nature protocol paper, unfortunately not open. (https://doi.org/10.1038/s41596-020-0342-4) It has the solution of common issues when running a funnel metadynamics simulation. (see some discussion in this post link)

PLUMED Masterclass 22.2: Analysis of Plumed output by Metadynminer

关键词 Keywords: Statistical analysis in R, MetaD
连结 Link: link
简评/备注 Comments/Remarks: include an exercise to make a movie of how the free energy surface was flooded MetaD with a single CV. Fill-in-the-blanks tutorial without answer but ok just numbers...

Lugano tutorial: Computing proton transfer in water

关键词 Keywords: CP2K, reaction
连结 Link: link
简评/备注 Comments/Remarks: proton transfer calculation with CP2K, simple one-step tutorial with example input. Finally not a Fill-in-the-blanks tutorial!

3.3.3. Umbrella sampling

PLUMED Masterclass 21.3: Umbrella sampling

关键词 Keywords: Gromacs, US, restraint, bias, PMF
连结 Link: link
简评/备注 Comments/Remarks: can be tricky to follow and adapt on one's own research, especially if not familiar with python.

3.3.4. Replica Exchange

PLUMED Masterclass 22.10: Hamiltonian replica exchange with PLUMED and GROMACS

关键词 Keywords: HREMD, gromacs, binless WHAM
连结 Link: link
简评/备注 Comments/Remarks: This is not a fill-in-the-blank tutorial, awesome! (1) plumed/gmx have to be compiled with MPI, not the internal thread-MPI in gromacs (2) Note the hardware rerquirement of replica excange.

Using Hamiltonian replica exchange with GROMACS

关键词 Keywords: HREMD, gromacs, REST2
连结 Link: link
简评/备注 Comments/Remarks: Additional documentation about the replica exchange implementation of the tutorial above (Masterclass 22.10)

3.3.5. Special CV

PLUMED Masterclass 22.5: Machine learning collective variables with Pytorch

关键词 Keywords: ML, AI, PyTorch, machine learning-based CVs
连结 Link: link
简评/备注 Comments/Remarks: Configure PLUMED with LibTorch and enable the PYTORCH and OPES modules following the instructions here. Files and solution are here. Answers are in ipynb.

PLUMED Masterclass 22.9: Using path collective variables to find reaction mechanisms in complex free energy landscapes

关键词 Keywords: path CV, MetaD, path-metadynamics, psemd
连结 Link: link
简评/备注 Comments/Remarks: If you just want to use the path CV, its easier to use the dimensionality reduction/path CV tutorials below or the documentation this path CV link. Fill-in-the-blank tutorial with solutions explanation in a yourtube video: link... Not ideal, I prefer a good example input file.

PLUMED Masterclass 21.6: Dimensionality reduction

关键词 Keywords: PCA, path CV, ASE, Gromacs
连结 Link: link
简评/备注 Comments/Remarks: This tutorial use a GUI interface chemiscope for PCA interactive view, may not be necessary if you are familiar with other tools. Fill-in-the-blanks tutorial with solution here

MARVEL tutorial: Path CVs

关键词 Keywords: PCA, path CV, Gromacs
连结 Link: https://www.plumed.org/doc-v2.9/user-doc/html/marvel-2.html
简评/备注 Comments/Remarks: older Path CV tutor with no fill-in-the-blank, more explanation, and does not use the chemiscope GUI

PLUMED Masterclass 22.12: Liquid-solid chemical potential differences with the environment similarity CV

关键词 Keywords: LAMMPS, environment similarity CV, OPES
连结 Link: link
简评/备注 Comments/Remarks: chemical potential differences between the liquid and a solid with the environment similarity CV. Not fill-in-the-blank!

Julich tutorial: Developing CVs in plumed

关键词 Keywords: CV, multicolvar
连结 Link: link
简评/备注 Comments/Remarks: Tutorial on how to implement new collective variables in plumed. Not fill-in-the-blank!

3.3.6. Others

PLUMED Masterclass 22.3: OPES method

关键词 Keywords: OPES, GROMACS 2020.6
连结 Link: link
简评/备注 Comments/Remarks: Need to compile plumed with OPES module and MPI enabled

PLUMED Masterclass 22.6: EDS module + Coarse-Grained directed simulations

关键词 Keywords: experiment directed simulation (EDS), psemd, gromacs
连结 Link: link
简评/备注 Comments/Remarks: bias collective variables to agree with set values. fill-in-the-blank tutorial with answers in link

PLUMED Masterclass 22.8: Modelling Concentration-driven processes with PLUMED

关键词 Keywords: gromacs, CmuMD, coordinationnumber, CV
连结 Link : link
简评/备注 Comments/Remarks: Gromacs+plumed compiled with CmuMD . analysis and simulation of processes driven by concentration.

PLUMED Masterclass 22.13: SASA module and the application of PLUMED for implicit solvent simulations

关键词 Keywords: SASA, CV, Amber, implicit solvent
连结 Link : link
简评/备注 Comments/Remarks: SASA module of PLUMED to perform implicit solvent simulations, run with sander module of Amber, has explanation on amber input. Script provided for gnuplot.

PLUMED Masterclass 22.15: FISST module and application of mechanical forces with PLUMED

关键词 Keywords: SMD, FISST, GROMACS, LAMMPS, PLUMED, pesmd
连结 Link : link
简评/备注 Comments/Remarks: need to enable fisst module when compiling plumed. Note: the github repo linked inside the tutorial is broken. Hence no solutions for the fill-in-the-blanks part.

PLUMED Masterclass 21.7: Optimizing PLUMED performances

关键词 Keywords: MetaD, Gromacs 2019.6, coordination number, SMOG
连结 Link : link
简评/备注 Comments/Remarks: fill-in-the-blank with answers in link

3.4. NAMD
3.4.1. Official NAMD tutorials at https://www.ks.uiuc.edu/Training/Tutorials/#freeenergymethods
(1) Some free energy methods only have GPU support after specific NAMD version

Protein:ligand Standard Binding Free Energies: A Tutorial for Alchemical and Geometrical Transformations

关键词 Keywords: Alchemical, FEP, ABF, colvars
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: this one has more theories than applications

A Tutorial on Alchemical Free Energy Perturbation Calculations in NAMD

关键词 Keywords: Alchemica, FEP, colvars
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: this one is clearer in terms of applications

A Tutorial on Adaptive Biasing Force Calculations in NAMD (multiple examples)

关键词 Keywords: ABF, FEP, Solvation free energy, CV, unfolding, isomerization, colvars
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: the solvation free energy tutorial compare FEP and ABF in calculating free energy, has a nice figure to illustrate.

Stretching Deca-Alanine:

关键词 Keywords: SMD, PMF, Interactive MD (IMD), VMD
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: IMD can be laggy, also will need to open port if the firewall block it.

Methods for calculating Potentials of Mean Force

关键词 Keywords: SMD, ABF, US, PMF, REMD, REMD-US, colvars
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: also has REMD-US in addition to standard US. Use Alan Grossfield's wham for reweighting.

A Tutorial on One-dimensional Replica-exchange Umbrella Sampling

关键词 Keywords: US, PMF, REMD, REUS, colvars
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: Use Alan Grossfield's wham for reweighting.

String Method with Swarms of Trajectories: A Tutorial for Free-energy Calculations along a Minimum-action Path

关键词 Keywords: ABF, colvars, path CV, PMF
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: path CV is also available in plumed

Exploring Complex Conformational Transition Pathways

关键词 Keywords: SMD, swarms of trajectories (SMwST), US, PMF, bias-exchange umbrella sampling, colvars
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: pull -> refine path -> sample -> get PMF

Adaptive Multilevel Splitting Method: Isomerization of Alanine Dipeptide

关键词 Keywords: colvars, Adaptive Multilevel Splitting (AMS) , flux
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: generally clear but harder to follow than other tutorials. From the perspective of a student, ABF tutorials are more well-written than this one.

Performing Metadynamics Simulations Using NAMD

关键词 Keywords: MetaD, WTM
连结 Link: Tutorial pdf link tutorial files link
简评/备注 Comments/Remarks: simple and concise, minimal information.

3.4.2. NAMD Tutorials published on LiveCoMS

Computing Absolute Binding Affinities by Streamlined Alchemical Free Energy Perturbation (SAFEP)

关键词 Keywords: FEP, Colvars, NAMD, VMD
连结 Link: LiveCoMS article https://doi.org/10.33011/livecoms.5.1.2067 github repo of tutorial files link
简评/备注 Comments/Remarks: generally clear

GaMD for NAMD (Example: Alanine dipeptide torsion)

关键词 Keywords: NAMD, GaMD
连结 Link: LiveCoMS article link github files link
简评/备注 Comments/Remarks: More comprehensive than the Amber GaMD tutorial on the developer's site. Same system: GaMD sampling of torsion, 3 forcefields (AMBER ff19SB, CHARMM36m, Drude-2019), provide additional analysis scripts to find and extract minima.

3.5. GROMOS

Tutorial in manual

关键词 Keywords: TI
连结 Link: link
简评/备注 Comments/Remarks: /

A Suite of Advanced Tutorials for the GROMOS Biomolecular Simulation Software [v2.0]

关键词 Keywords: TI, alchemical, HREMD, selective GaMD, GROMOS11 1.6.1
连结 Link: LiveCoMS article link github repo of tutoral files link
简评/备注 Comments/Remarks: /

3.6. OpenMM
(1) OpenMM is commonly used via the Python interface.
(2) There are some 3rd-party tutorials that use OpenMM for the python interface, skipping them for now and only list official free energy tutorials here.

Alchemical free energy calculations (Computing the free energy of inserting a Lennard-Jones particle in a Lennard-Jones fluid)

关键词 Keywords: TI, alchemical
连结 Link: link
简评/备注 Comments/Remarks: Simple model system, also in OpenMM 7 publication link

Umbrella sampling (Free energy of pulling a deca-alanine helix into a coil in vacuum)

关键词 Keywords: US, PMF
连结 Link: link
简评/备注 Comments/Remarks: Small system, vacuum

Run a REST simulation (Example: villin in water)

关键词 Keywords: REMD, Replica exchange solute tempering (REST)
连结 Link: link
简评/备注 Comments/Remarks: Small system, explicit water

3.7. WESTPA (The Weighted Ensemble Simulation Toolkit with Parallelization and Analysis)
(1) a python toolkit, can interface Amber, Gromacs, OpenMM, NAMD
(2) 注意：教程明文写出部分WESTPA方法应用的I/O频率会对普通Gaming GPU 造成损耗。

Github wiki with links to all tutorials

关键词 Keywords: WE
连结 Link:link
简评/备注 Comments/Remarks:TOC page linking to generic tutorials and example files for different supporting MD engine.

LiveCoMS Tutorials

A Suite of Tutorials for the WESTPA 2.0 Rare-Events Sampling Software [Article v2.0]

关键词 Keywords: WE
连结 Link: LiveCoMS v2 link
简评/备注 Comments/Remarks: Clear, well-written with comprehensive examples. Compared to the v1.0 article it is more organized with additional examples. Sadly because of the warnings on potential GPU damage, I haven't tried it before. Can't take the risk.

A Suite of Tutorials for the WESTPA Rare-Events Sampling Software [Article v1.0]

关键词 Keywords: WE
连结 Link: LiveCoMS v1 link
简评/备注 Comments/Remarks: Clear, well-written with comprehensive examples. Because of the warnings on potential GPU damage, I haven't tried it before. Can't take the risk.

4. Related websites or tools
Colvars User Manual

Gromacs link
VMD link
NAMD link

Plumed User Manual

Link to all major plumed versions: link

All LiveCoMS tutorials

LiveCoMS tutorial articles link

Generic WHAM reweighting (1d and 2d)

Alan Grossfield's wham link

Other collections mostly related to alchemical / FEP methods

PyAutoFEP link
A wiki of alchemical methods link
FreeSolv database link
(EOL) alchemical analysis python link
alchemical analysis python library link
Numerous FEP/TI/ABFE tutorials rely too much on 3rd-party python libraries, instead of using the MD code directly (e.g. biosimspace tutorial link FEP part link) thus skipping
(old, deprecated toolkit: FESetup, skipping links)

5. 结语
以上分享了自用的网上公开免费自由能/增强采样教程连结，希望能帮到大家。

由于这只是一个自用的整理，恕不回应任何教程使用相关问题，请另外开帖或咨询原作者。

如果有好的教程建议、补充欢迎留言分享。如果以上教程连结失效/内容过分误导需移除也请告诉我。

作者
Author: jzeng 时间: 2025-10-7 08:33

作者
Author: HNUST 时间: 2025-10-7 13:39
太好了，支持，为新手指引了道路，现在良莠不齐的教程太多了，是时候出个标准的了

作者
Author: Daniel_Arndt 时间: 2025-10-7 15:00
WESTPA的教程为什么更新工作做得比较好，估计跟Anthony Bogetti当时负责这事有关。他太nice了，他PhD defense时有人专门在open door session这个环节感谢他当年做助教时细致认真。

作者
Author: youyno 时间: 2025-10-8 05:51
添加一个我们课题组开发的用于自由能处理的Python程序ThermoLib。https://github.ugent.be/pages/lvduyfhu/ThermoLIB/index.html

作者
Author: student0618 时间: 2025-10-8 11:51
本帖最后由 student0618 于 2025-10-8 12:34 编辑

youyno 发表于 2025-10-8 05:51
添加一个我们课题组开发的用于自由能处理的Python程序ThermoLib。https://github.ugent.be/pages/lvduyfhu/ ...

感谢提供! 由于要申请并非完全open先不放在主帖，有兴趣的朋友可参考以下连结及获取方法
https://molmod.ugent.be/software/thermolib
(图片的github 页面 404 error，是access不公开repo常见的；而楼上的github网址要登入)

(, 下载次数 Times of downloads: 0)

作者
Author: Daniel_Arndt 时间: 2025-11-3 11:34
plumed里面的REST2教程我之前用过 https://www.plumed.org/doc-v2.9/user-doc/html/hrex.html ，写得还行。

作者
Author: student0618 时间: 2025-11-3 11:57
本帖最后由 student0618 于 2025-11-3 12:12 编辑

Daniel_Arndt 发表于 2025-11-3 11:34
plumed里面的REST2教程我之前用过 https://www.plumed.org/doc-v2.9/user-doc/html/hrex.html ，写得还行。

谢谢补充，已补上至第3.3.4节。

关键词List of abbreviations加上了 REST/REST1/REST2 Hamiltonian scaling in Replica Exchange with Solute Tempering

作者
Author: student0618 时间: 2025-11-19 10:13
Justin的旧FEP教程名字更改为Free Energy of van der Waals transformation，还终于加了个比较实际的Free Energy of Hydration 教程 (有VdW+Coulomb transform 不过用31个Lambda)

最近较忙没时间细看及测试，如果发现问题请通知我。

居然还有个Coming soon的Binding free energy (of protein-ligand complex) 但没说方法，先观望一下，如果是ABFE再放。

欢迎光临计算化学公社 (http://bbs.keinsci.com/)