In this tutorial we will perform a simulation with the popular NAMD molecular dynamics software. Please note NAMD tools are not currently available on a public Galaxy server due to licensing issues. If you are interested in following this tutorial, you will need to download the BRIDGE docker container and download NAMD yourself.

Agenda

In this tutorial, we will cover:

1. System preparation with CHARMM
   1. Setup
2. MD simulations with NAMD
3. Workflows
4. Conclusion

This tutorial is made up of two parts. In the first section, we will look at preparation of a system (solvation, charge neutralisation, energy minimisation) using CHARMM. In the second section, we will perform an equilibration and production simulation, using NAMD. If you already completed the Setting up molecular systems tutorial, which covers the use of the CHARMM graphical user interface (GUI), you have already prepared your system, so go straight to the second section, using the files you prepared earlier.

The process can be accomplished by selecting each tool from the tools menu, or by importing the workflow. The workflow method is most efficient and the individual tools used in the workflows are discussed below. The entire workflow (preparation + simulation) is shown below for CHARMM and NAMD.

Details: NVT, NPT and statistical mechanics theory

See Statistical Mechanics, McQuarrie for more in depth theory ISBN:9781891389153

System preparation with CHARMM

If you already prepared your system using the CHARMM-GUI, and saved the output files, you can skip this section.

Setup

Initially, we need to prepare a protein-ligand system in CHARMM.

This tool will:

• solvate the protein-ligand complex, using the TIP3P water model
• neutralise the system, using 0.05M NaCl
• conduct a short energy minimisation

Hands-on: Data upload

1. Create a new history for this tutorial.

   Tip: Creating a new history

   To create a new history simply click the new-history icon at the top of the history panel:

   

2. Import the files from the Zenodo link provided.

   https://zenodo.org/record/3234841/files/cbh1test.crd
   https://zenodo.org/record/3234841/files/cbh1test.psf
   

   Tip: Importing via links

   • Copy the link location

   • Click galaxy-upload Upload Data at the top of the tool panel

   • Select galaxy-wf-edit Paste/Fetch Data

   • Paste the link(s) into the text field

   • Press Start

   • Close the window

   Tip: Importing data from a data library

   As an alternative to uploading the data from a URL or your computer, the files may also have been made available from a shared data library:

   1. Go into Data (top panel) then Data libraries
   2. Navigate to the correct folder as indicated by your instructor.
      • On most Galaxies tutorial data will be provided in a folder named GTN - Material –> Topic Name -> Tutorial Name.
   3. Select the desired files
   4. Click on Add to History galaxy-dropdown near the top and select as Datasets from the dropdown menu

   5. In the pop-up window, choose

      • “Select history”: the history you want to import the data to (or create a new one)
   6. Click on Import

3. Rename the datasets.

   Tip: Renaming a dataset

   • Click on the galaxy-pencil pencil icon for the dataset to edit its attributes
   • In the central panel, change the Name field
   • Click the Save button

4. Check that the datatype is correct. The crd file should have the CRD datatype and the psf file the PSF datatype.

   Tip: Changing the datatype

   • Click on the galaxy-pencil pencil icon for the dataset to edit its attributes
   • In the central panel, click galaxy-chart-select-data Datatypes tab on the top
   • In the galaxy-chart-select-data Assign Datatype, select datatypes from “New type” dropdown
     • Tip: you can start typing the datatype into the field to filter the dropdown menu
   • Click the Save button

Hands-on: initial processing

Run System Setup tool with the following parameters:

• param-file “psf input”: Protein structure file of the protein-ligand system. (Input dataset)
• param-file “crd input”: Coordinate file of the protein-ligand system. (Input dataset)
• “Buffer”: Edge to edge distance between the protein and the edge of the water box in angstroms
• “Custom topology and parameter files for ligands” (optional)

Energy minimisation

The setup provides us with the CRD and PSF files needed to perform a simulation. In addition, we have a PRM file which defines the parameters of the unit cell. Now, we need to perform energy minimisation. This relaxes the system, removing any steric clashes or unusual geometry which could artificially raise the energy.

This tools will:

• Minimise energy using a steepest descent algorithm followed by Adopted Newton Raphson (using the defined number of steps)
• Set up periodic boundaries and generate Particle Mesh Ewald (PME)
• generate reference structures for restraints in NAMD (if selected)

Hands-on: energy minimization

Run Energy Minimizer tool with the following parameters:

• param-file “system_setup_crd”: Coordinate file generated by the setup tool. (Input dataset)
• param-file “system_setup_psf”: Protein structure file generated by the setup tool. (Input dataset)
• param-file “waterbox parameters input”: Water box parameter file generated by the setup tool. (Input dataset)
• “Minimization steps”: 1000
• “Create reference structures for RMSD restraints for NAMD?”: No
• “Custom topology and parameter files for ligands”: No

MD simulations with NAMD

At this point we are ready to run the simulation, which uses NAMD as a molecular dynamics engine. An NVT simulation is followed by an NPT simulation.

NVT

Classical NVT dynamics, maintaining constant number of particles, volume and temperature.

This tool runs classical molecular dynamics simulations in NAMD using an NVT ensemble. User can run the simulation in small time intervals. The coordinates, velocities and the extended system files can be use to restart the simulations. If required, harmonic restraints can be used to maintain the protein shape. These restraints, in particular RMSD harmonic restraints can be added with the NAMD collective variable module.

Hands-on: NVT dynamics

1. NAMD MD Simulator (NVT) tool with the following parameters:
   • param-file “xplor psf input”: PSF file from CHARMM preparation (Input dataset)
   • param-file “pdb input”: PDB file from CHARMM preparation (Input dataset)
   • param-file “PME grid specs”: Generated by the setup tool (Input dataset)
   • param-file “waterbox prm input”: Water box parameter file generated by the setup tool. (Input dataset)
   • “Temperature (K)”: 300
   • “Are you restarting a simulation?”: No
   • “Use Harmonic restraints simulation?”: No
   • “Custom parameter file for ligands”: No
   • “DCD Frequency (ps)”: 1 (Frequency to record frames in the DCD trajectory)
   • “Simulation Time (ps)”: 10
   • “Number of processors”: 4

NPT

Classical NPT dynamics, maintaining constant number of particles, pressure and temperature.

This tool runs classical molecular dynamics simulations in NAMD using an NPT ensemble. User can run the simulation in small time intervals. The coordinates, velocities and the extended system files can be use to restart the simulations. Harmonic restraints can be used. NAMD collective variable module is used to give RMSD harmonic restraints.

Hands-on: NPT dynamics

1. NAMD MD Simulator (NPT) tool with the following parameters:
   • param-file “xplor psf input”: PSF file from CHARMM preparation (Input dataset)
   • param-file “pdb input”: PDB file from CHARMM preparation (Input dataset)
   • param-file “PME grid specs”: Generated by the setup tool (Input dataset)
   • param-file “waterbox prm input”: Water box parameter file generated by the setup tool. (Input dataset)
   • “Temperature (K)”: 300
   • “Pressure (bar)”: 1.01325
   • “Are you restarting a simulation?”: Yes
   • “Coordinates from the previous simulation”: from the NVT simulation
   • “Velocities from the previous simulation”: from the NVT simulation
   • “Extended system of the previous simulation”: from the NVT simulation
   • “Use Harmonic restraints simulation?”: No
   • “Custom parameter file for ligands”: No
   • “DCD Frequency (ps)”: 1 (Frequency to record frames in the DCD trajectory)
   • “Simulation Time (ps)”: 15
   • “Number of processors”: 4

Workflows

Both the CHARMM preparatory workflow and the NAMD simulation workflow are available as an alternative to executing individual tools.

Open image in new tab

Open image in new tab

Conclusion

After completing the steps, or running the workflow, we have successfully produced a trajectory (the xtc file) which describes the atomic motion of the system. This can be viewed using molecular visualization software or analysed further; please visit the visualization and analysis tutorials for more information.

You've Finished the Tutorial

Please also consider filling out the Feedback Form as well!

Key points

• Several MD engines are available in BRIDGE

• Workflows are available for common simulations tasks such as equilibration and production dynamics for various ensembles (NVT, NPT)

• You’ve run an equilibrium and production MD simulation using NAMD

Frequently Asked Questions

Useful literature

Further information, including links to documentation and original publications, regarding the tools, analysis techniques and the interpretation of results described in this tutorial can be found here.

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Citing this Tutorial

1. Christopher Barnett, Tharindu Senapathi, Simon Bray, Running molecular dynamics simulations using NAMD (Galaxy Training Materials). https://training.galaxyproject.org/training-material/topics/computational-chemistry/tutorials/md-simulation-namd/tutorial.html Online; accessed TODAY
2. Hiltemann, Saskia, Rasche, Helena et al., 2023 Galaxy Training: A Powerful Framework for Teaching! PLOS Computational Biology 10.1371/journal.pcbi.1010752
3. Batut et al., 2018 Community-Driven Data Analysis Training for Biology Cell Systems 10.1016/j.cels.2018.05.012

BibTeX

@misc{computational-chemistry-md-simulation-namd,
author = "Christopher Barnett and Tharindu Senapathi and Simon Bray",
	title = "Running molecular dynamics simulations using NAMD (Galaxy Training Materials)",
	year = "",
	month = "",
	day = "",
	url = "\url{https://training.galaxyproject.org/training-material/topics/computational-chemistry/tutorials/md-simulation-namd/tutorial.html}",
	note = "[Online; accessed TODAY]"
}
@article{Hiltemann_2023,
	doi = {10.1371/journal.pcbi.1010752},
	url = {https://doi.org/10.1371%2Fjournal.pcbi.1010752},
	year = 2023,
	month = {jan},
	publisher = {Public Library of Science ({PLoS})},
	volume = {19},
	number = {1},
	pages = {e1010752},
	author = {Saskia Hiltemann and Helena Rasche and Simon Gladman and Hans-Rudolf Hotz and Delphine Larivi{\`{e}}re and Daniel Blankenberg and Pratik D. Jagtap and Thomas Wollmann and Anthony Bretaudeau and Nadia Gou{\'{e}} and Timothy J. Griffin and Coline Royaux and Yvan Le Bras and Subina Mehta and Anna Syme and Frederik Coppens and Bert Droesbeke and Nicola Soranzo and Wendi Bacon and Fotis Psomopoulos and Crist{\'{o}}bal Gallardo-Alba and John Davis and Melanie Christine Föll and Matthias Fahrner and Maria A. Doyle and Beatriz Serrano-Solano and Anne Claire Fouilloux and Peter van Heusden and Wolfgang Maier and Dave Clements and Florian Heyl and Björn Grüning and B{\'{e}}r{\'{e}}nice Batut and},
	editor = {Francis Ouellette},
	title = {Galaxy Training: A powerful framework for teaching!},
	journal = {PLoS Comput Biol}
}

                   

Go Further

Do you want to extend your knowledge? Follow one of our recommended follow-up trainings:

• tutorial Hands-on: Analysis of molecular dynamics simulations

Galaxy Administrators: Install the missing tools

You can use Ephemeris's shed-tools install command to install the tools used in this tutorial.

shed-tools install [-g GALAXY] [-a API_KEY] -t <(curl https://training.galaxyproject.org/training-material/api/topics/computational-chemistry/tutorials/md-simulation-namd/tutorial.json | jq .admin_install_yaml -r)

Alternatively you can copy and paste the following YAML

---
install_tool_dependencies: true
install_repository_dependencies: true
install_resolver_dependencies: true
tools: []

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