Connect with us

MD Simulation

How to generate topology of small molecules & ligands for MD Simulation?

Dr. Muniba Faiza

Published

on

generate topology of small molecules & ligands for MD simulation

Generating the topology of small molecules/ligands is an important step in molecular dynamics (MD) Simulation. We explained it in previous articles as part of MD simulation tutorials. In this article, we will explain how can you generate the topology of ligands for MD simulation of complex or small molecules only.

We are going to generate topologies of small molecules for their MD simulation and for the ligands that are present in complexes that are further subjected to MD simulation.

A) For small-molecule MD simulation

1. Obtaining the molecule

If your molecule is available in Pubchem, then download the 3D structure in .sdf format. Otherwise, you will have to draw one. For that, you can use software such as ChemDraw, Marvinsketch, etc.

1.1. Downloading structure from Pubchem

  1. Go to Pubchem.
  2. Search for a molecule/compound of your interest.
  3. Click on the ‘Download‘ button.
  4. Download the 3D conformer in SDF format.

We need the structure in the PDB format. For this purpose, use Pymol as shown below.

  1. Go to File --> Open. Select the molecule downloaded in SDF format.
  2. Go to Export Molecule --> PDB Options --> Write CONECT records for all bonds. You can deselect the next checkbox (i.e., ‘Write segment identifier (segi) column‘).
  3. Click Save. Select PDB from file type dropdown.

Now you have generated the PDB file of your molecule successfully.

1.2. Drawing the structure

To draw a molecular structure, you can use Pymol, Avogadro, Chemdraw, and so on. In this tutorial, we will be using Pymol [1]. Follow this tutorial for building molecules in Pymol. Don’t forget to export your molecule in PDB format.

2. Preparing the molecule

Now that we have our molecule in PDB, we can easily convert this molecule in mol2 format. For this purpose, we will use Avogadro [2, 3].

Note: Since this tutorial is based on the generation of topology using CGenFF, therefore, the force field required for MD simulation will be CHARMM. If you are going to use any other force field, then you will have to use another webserver for topology generation. To know about these webservers, read this article.

  1. Open Avogadro
  2. Open --> molecule.pdb
  3. Go to Build --> Add Hydrogens
  4. Go to File --> Save as --> SYBYL mol2
  5. Save it as molecule.mol2.

2.1. Correcting mol2 file

Now, before generating the topology of this molecule, we need to correct this mol2 file.

Open the molecule.mol2 file in an editor and do the following:

  1. Replace “*****” with molecule name (it can be any short name of the molecule). The detailed figures are shown in previous article.
  2. Make sure the residue name and numbers are the same.
  3. Look into the @<TRIPOS>BOND section. Now correct the bond order using a Perl script available here.
  4. Run the Perl script as $ perl sort_mol2_bonds.pl molecule.mol2 molecule_clean.mol2

This file (molecule_clean.mol2) can finally be used to generate topology.

3. Generating topology of small molecule

Register and create a free account on the CGenFF server [4]. After uploading and submitting your clean file, it will give an output .str file (in this case, molecule_clean.str). Download this file.

Now you need to convert this .str file in gmx format to use in GROMACS for simulation. For that, download the “cgenff_charmm2gmx.py” script from here and run it as shown below. If you have python3 installed on your system, then use another script. Download it from here. Remember it also requires another package called NetworkX.

$ python cgenff_charmm2gmx.py <molecule_name> molecule_clean.mol2 molecule_clean.str charmm36-jul2020.ff

You will find two new files in your working directory: molecule.itp molecule.prm.

B) For a complex simulation

1. Extracting the ligand

Let’s suppose our protein filename is protein.pdb. Open a terminal (Ctrl+Alt+T) and type the following command:

$ grep ligand_name protein.pdb > ligand.pdb

Now, remove all ligand’s name lines from the protein.pdb file.

2. Preparing the ligand file

Now you will need this ligand.pdb file in mol2 format. For that, you can follow the same steps as shown above for small molecules under the section of ‘Preparing the molecule‘ (section 2.).

2.1. Correcting the ligand file

To correct the ligand file, you can follow the same procedure as shown above in section 2.1. After you have successfully, corrected your ligand file (ligand_clean.mol2), you can proceed to topology generation of the ligand.

3. Generating the topology of ligand

Upload your corrected mol2 file on the CGenFF server and wait for the resultant file (ligand_clean.str). Further, correct your .str file using the following command:

$ python cgenff_charmm2gmx.py ligand_name ligand_clean.mol2 ligand_clean.str charmm36-jul2020.ff

Now, you have successfully generated the topology of your ligand. For further steps on MD simulation of a protein-ligand complex, read this tutorial.


References

  1. The PyMOL Molecular Graphics System, Version 1.2r3pre, Schrödinger, LLC.
  2. Avogadro: an open-source molecular builder and visualization tool. Version 1.XX. http://avogadro.cc/
  3. Marcus D Hanwell, Donald E Curtis, David C Lonie, Tim Vandermeersch, Eva Zurek and Geoffrey R Hutchison; “Avogadro: An advanced semantic chemical editor, visualization, and analysis platform” Journal of Cheminformatics 2012, 4:17.
  4. Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., … & Mackerell Jr, A. D. (2010). CHARMM general force field: A force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields. Journal of computational chemistry31(4), 671-690.

Dr. Muniba is a Bioinformatician based in New Delhi, India. She has completed her PhD in Bioinformatics from South China University of Technology, Guangzhou, China. She has cutting edge knowledge of bioinformatics tools, algorithms, and drug designing. When she is not reading she is found enjoying with the family. Know more about Muniba

Bioinformatics Programming

Free_Energy_Landscape-MD: Python package to create Free Energy Landscape using PCA from GROMACS.

Dr. Muniba Faiza

Published

on

In molecular dynamics (MD) simulations, a free energy landscape (FEL) serves as a crucial tool for understanding the behavior of molecules and biomolecules over time. It is difficult to understand and plot a meaningful FEL and then extract the time frames at which the plot shows minima. In this article, we introduce a new Python package (Free_Energy_Landscape-MD) to generate an FEL based on principal component analysis (PCA) from MD simulation done by GROMACS [1].

(more…)

Continue Reading

MD Simulation

[Tutorial] Installing VIAMD on Ubuntu (Linux).

Dr. Muniba Faiza

Published

on

[Tutorial] Installing VIAMD on Ubuntu (Linux).

Visual Interactive Analysis of Molecular Dynamics (VIAMD) is a tool that allows the interactive analysis of molecular dynamics simulations [1]. In this article, we are installing it on Ubuntu (Linux).

(more…)

Continue Reading

MD Simulation

Energy minimization and equilibration of simple protein using NAMD & VMD.

Dr. Muniba Faiza

Published

on

Energy minimization and equilibration of simple protein using NAMD & VMD.

In this tutorial, we will perform energy minimization and equilibration of a simple protein using NAMD [1] & VMD [2]. We are using insulin (PDB ID: 2wfu) for this tutorial.

(more…)

Continue Reading

MD Simulation

Generating topology of molecule for AMBER forcefield for GROMACS.

Dr. Muniba Faiza

Published

on

Generating topology of molecule for AMBER forcefield for GROMACS.

In this article, we will generate the topology of a small molecule for AMBER forcefield to be used in MD simulation using GROMACS.

(more…)

Continue Reading

MD Simulation

How to visualize output plots of MD simulation (GROMACS)?

Dr. Muniba Faiza

Published

on

How to visualize output plots of MD simulation (GROMACS)?

Visualizing plots of molecular dynamics simulation is easy once you have generated them. Previously, we provided a few articles on MD output analysis (check the Further Reading section). This article explains how you can easily visualize the plots generated from GROMACS output. (more…)

Continue Reading

MD Simulation

How to solve ‘Could NOT find CUDA: Found unsuitable version “10.1”‘ error during GROMACS installation?

Dr. Muniba Faiza

Published

on

How to solve ‘Could NOT find CUDA: Found unsuitable version “10.1”‘ error during GROMACS installation?

Compiling GROMACS [1] with GPU can be trivial. Previously, we have provided a few articles on the same. In this article, we will solve an error frequently occurring during GROMACS installation.

(more…)

Continue Reading

MD Simulation

How to calculate number of steps (nsteps) for MD simulation run?

Dr. Muniba Faiza

Published

on

How to calculate number of steps (nsteps) for MD simulation run?

While doing molecular dynamics (MD) simulation, it can be difficult to calculate the number of steps or nsteps for an MD run accurately. In this article, we will learn to calculate nsteps for an MD run. (more…)

Continue Reading

MD Simulation

How to install GROMACS on Apple M1 (MacOS)?

Dr. Muniba Faiza

Published

on

Installing GROMACS on Apple M1 (MacOS)

We have provided a few articles on GROMACS installation on Ubuntu. In this article, we are going to install GROMACS [1] on Mac OS. (more…)

Continue Reading

MD Simulation

How to take snapshots of structure at specific times in GROMACS?

Published

on

How to take snapshots of structure at specific times in GROMACS?

It is important to see the behavior of protein during an MD simulation. This can be achieved by taking snapshots in the form of PDB format. In this article, we have provided a few commands that you can use to take snapshots of a complete system or protein during MD simulation. (more…)

Continue Reading

MD Simulation

GROMACS: Uses & Applications

Dr. Muniba Faiza

Published

on

GROMACS: Uses & Applications

GROMACS stands for GROningen MAchine for Chemical Simulations [1]. It is a very popular and one of the most widely used open-source bioinformatics software. It is generally used for molecular dynamics simulation of macromolecules. In this article, we will explain its uses and applications in bioinformatics studies. (more…)

Continue Reading

MD Simulation

Easy installation of GROMACS on Ubuntu 18.04 & 20.04

Dr. Muniba Faiza

Published

on

Installing GROMACS on ubuntu

We have provided several articles on GROMACS [1] installation on Ubuntu including the easy installation method for GROMACS version 5.x.x. In this article, we will provide shell scripts to install the latest (2021 series) of GROMACS on Ubuntu 18.04 and 20.04. (more…)

Continue Reading

MD Simulation

How to create an index file in GROMACS for MD simulation?

Dr. Muniba Faiza

Published

on

How to create an index file in GROMACS for MD simulation?

MD simulation is a tricky technique if you don’t understand what you are doing through various parameters and algorithms in GROMACS [1]. That may lead to several errors. In this article, we are going to create an index file for the protein groups in GROMACS to solve such errors. (more…)

Continue Reading

MD Simulation

Tutorial: MD Simulation of small organic molecules using GROMACS

Dr. Muniba Faiza

Published

on

MD Simulation of small molecules

GROMACS [1] offers a vast range of functions when it comes to molecular dynamics simulation. Today, we are going to explore it for the simulation of small organic molecules. (more…)

Continue Reading

MD Simulation

Tutorial: MD simulation with mixed solvents using GROMACS

Dr. Muniba Faiza

Published

on

MD simulation with mixed solvents

In this tutorial, we are performing MD simulation in mixed solvents of methanol and water using GROMACS [1,2]. You can follow our previous articles for MD simulation of a simple protein and a protein-ligand complex. (more…)

Continue Reading

MD Simulation

Tutorial: MD simulation output analysis of a complex using GROMACS

Dr. Muniba Faiza

Published

on

MD simulation output analysis of a complex using GROMACS

We have provided several tutorials on molecular dynamics (MD) simulation (please check further reading section). They include installation of simulation software, simulation of a simple protein, and a complex. In this article, we will analyze the GROMACS [1] output of MD simulation of a complex. (more…)

Continue Reading

MD Simulation

How to submit MD simulation job on a cluster server using PBS script?

Dr. Muniba Faiza

Published

on

MD Simulation on cluster server

Molecular dynamics (MD) simulation is one of the most widely used methods in bioinformatics. It needs high computation time and therefore, performed on workstations and servers. It requires software to upload and download files to and from the server. In this article, we have explained how to submit MD simulation jobs on cluster computers using PBS scripts. (more…)

Continue Reading

MD Simulation

Method-1: Installing GROMACS on Ubuntu with CUDA GPU Support

Dr. Muniba Faiza

Published

on

Install gromacs with gpu acceleration

GROMACS [1] is one of the most popular software in bioinformatics for molecular dynamic (MD) studies of macromolecules. We have provided different tutorials regarding MD simulation using GROMACS including its installation on Ubuntu. In this article, we will install GROMACS with GPU acceleration. (more…)

Continue Reading

MD Simulation

Installing GROMOS96 on Ubuntu

Dr. Muniba Faiza

Published

on

Installing gromos96 on Ubuntu

GROMOS96 is a well-known software package used for biomolecular simulations [1]. It can be used for the molecular dynamics simulation of protein, peptide, and protein-ligand complex as well. In this article, we will install GROMOS96 on Ubuntu. (more…)

Continue Reading

MD Simulation

MD Simulation using GROMACS: Things to remember

Dr. Muniba Faiza

Published

on

MD Simulation

Molecular dynamics (MD) simulation is considered amongst the important methods in bioinformatics. Installation of MD simulation software and execution of their commands is critical. It requires several parameters to be considered before performing simulations. A single mistake may result in impractical outputs. In this article, we will discuss such important things to remember during the MD simulation and installation and execution of its software (GROMACS) [1,2]. (more…)

Continue Reading

MD Simulation

Video Tutorial: MD Simulation using GROMACS

Dr. Muniba Faiza

Published

on

Video Tutorial: MD simulation using GROMACS

This is a video tutorial of our existing article “Molecular Dynamics (MD) Simulation using GROMACS“.

Continue Reading

LATEST ISSUE

ADVERT