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Tutorial: MD simulation with mixed solvents using GROMACS

Dr. Muniba Faiza

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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.

Download a structure of your protein of interest from PDB. In this tutorial, we are going to simulate insulin (PDB ID: 1ZNI).

1. Preparing protein file

Remove the other chains and hetatoms including the water molecules (HOH) from the protein file. You can use an editor such as vim, notepadqq in Ubuntu, and notepad++ in Windows. You can also use the following command to remove the hetatoms:

$ grep -v HETATM 1zni.pdb > 1zni_new.pdb

2. Converting PDB to gmx and generating topology

pdb2gmx module generates the topology of proteins. Make sure the protein file consists of protein atoms only otherwise it will be giving errors.

$ gmx pdb2gmx -f 1zni_new.pdb -o 1zni_processed.gro -water spce

It will ask to select the force field that contains information to be written to the topology. This an important step, therefore, select an appropriate field relevant to your study. In this tutorial, we will be using the OPLS all-atom force field, so type 15 in the terminal.

Now, you have three new files: 1zni_processed.gro, posre.itp, and topol.top.

For details on these commands/steps, please read our previous articles mentioned above.

3. Defining box

In order to build a system, we need to define a box of proper dimensions for the protein. You can choose different types of boxes but here we will be using a rhombic dodecahedron box as it can save the number of water molecules during the solvation of protein (discussed in the next step). editconf module will be used for defining the box.

$ gmx editconf -f 1zni_processed.gro -o 1zni_box.gro -c -d 3.0 -bt dodecahedron

Now, we have successfully defined the box around the protein. Let’s move on to the next step.

4. Solvating the protein

4.1. Fill with methanol

At first, we will fill the box with methanol. We are going to use the gmx insert-molecules module for adding methanol molecules to the box. For that, you need an itp file and gro file of methanol. Download methanol.itp and methanol.gro files. Determine how many molecules you have to add to the box according to the concentration and ratio to the water. Here, I am adding 30 molecules.

$ gmx insert-molecules -f 1zni_box.gro -ci methanol.gro -nmol 30 -try 20 -o 1zni_methanol_box.gro

4.1. Fill with water

To fill the rest of the box with water, you can either use the above gmx insert-molecules module or use gmx solvate as shown below. For the former, you will need another gro file for this solvent.

$ gmx solvate -cp 1zni_methanol_box.gro -cs spc216.gro -o 1zni_mixed_solvate.gro -p topol.top

Look at the input box files. First, we created a box around the protein, then filled it with methanol, and later with water.

Now open topol.top file in an editor and add the number of molecules of methanol in the [molecules] directive. Then, include methanol.itp file as shown below:

#include "oplsaa.ff/ions.itp"

#include "methanol.itp"

Save topol.top file.

In the next step, you might get some errors regarding the number of atoms being different in the topology file and gro file. Check your number of added solvent molecules (methanol+water).

Now, proceed with the rest of the simulation steps mentioned in the previous articles.


References

  1. Abraham, M. J., Murtola, T., Schulz, R., Páll, S., Smith, J. C., Hess, B., & Lindahl, E. (2015). GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX1, 19-25.
  2. Abraham, M. J., Van Der Spoel, D., Lindahl, E., & Hess, B. (2015). the GROMACS Development Team (2014) GROMACS User Manual Version 5.0. 4.

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

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