The OSF is a series of tutorials provided to get an idea of the language and programs that we commonly use in our lab and to show you how we train our undergraduate research students. Understand what the command does and how you can utilize it; do not just type it in and move forward without understanding. This will greatly benefit you in the future. You must complete all tutorials before moving into your own research; however, this does not mean you cannot begin searching the literature about your project and briefly learning more while doing tutorials.

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Lysozyme in Water. Corrosion Inhibition b Analysis and Simulatio Structure and stabilit Each step will contain an explanation of input and output, using typical settings for general use. Start the tutorial! Once you have downloaded the structure, you can visualize the structure using a viewing program such as VMD, Chimera, PyMol, etc. Once you've had a look at the molecule, you are going to want to strip out the crystal waters.

Do not word processing software! Note that such a procedure is not universally appropriate i. Always check your. Terminal regions may be absent, and may not present a problem for dynamics.

Incomplete internal sequences or any amino acid residues that have missing atoms will cause pdb2gmx to fail. Also note that pdb2gmx is not magic. The topology topol. This information includes nonbonded parameters atom types and charges as well as bonded parameters bonds, angles, and dihedrals. We will take a more detailed look at the topology once it has been generated. Execute pdb2gmx by issuing the following command: pdb2gmx -f 1AKI. This is a very important choice!

You should always read thoroughly about each force field and decide which is most applicable to your situation. For this tutorial, we will use the all-atom OPLS force field, so type 5 at the command prompt, followed by 'Enter'. There are many other options that can be passed to pdb2gmx. Some are listed here:? The topol. The posre. Again, using a plain text editor, inspect its contents. After several comment lines preceded by ; , you will find the following: include "ffoplsaa.

It is at the beginning of the file, indicating that all subsequent parameters are derived from this force field. There are 3 exclusions for bonded neighbors. The next section defines the [ atoms ] in the protein. Subsequent sections include [ bonds ], [ pairs ], [ angles ],and [ dihedrals ]. Some of these sections are self-explanatory bonds, angles, and dihedrals. Special interactions are included under "pairs" section 5. The "posre. The remainder of the topology file is dedicated to defining other molecules and providing system-level descriptions.

We chose this by passing "-water spce" to pdb2gmx. For an excellent summary of the many different water models, click here, but be aware that not all of these models are present within GROMACS. Ion parameters are included next: ; Include generic topology for ions include "ions. The [ molecules ] directive lists all of the molecules in the system, in the order that they appear in the coordinate.

Now that we have examined the contents of a topology file, we can continue building our system. In this example, we are going to be simulating a simple aqueous system. It is possible to simulate proteins and other molecules in different solvents, provided that good parameters are available for all species involved. There are two steps to defining the box and filling it with solvent: 1 Define the box dimensions using editconf.

You are now presented with a choice as to how to treat the unit cell. For the purpose of this tutorial, we will use a simple cubic box as the unit cell.

The box type is defined as a cube -bt cubic. The distance to the edge of the box is an important parameter. Since we will be using periodic boundary conditions, we must satisfy the minimum image convention. That is, a protein should never see its periodic image, otherwise the forces calculated will be spurious.

Specifying a solute-box distance of 1. This distance will be sufficient for just about any cutoff scheme commonly used in simulations. Now that we have defined a box, we can fill it with solvent water.

We are using spc You can use spc Note the changes to the [ molecules ] directive of topol. If you missed this information in the pdb2gmx output, look at the last line of your [ atoms ] directive in topol. What genion does is read through the topology and replace water molecules with the ions that the user specifies. The input is called a run input file, which has an extension of.

What grompp does is process the coordinate file and topology which describes the molecules to generate an atomic-level input. To produce a. An example. In reality, the. I typically use an energy-minimization script, because they are very basic and do not involve any complicated parameter combinations. Assemble your. We will pass this file to genion: genion -s ions. You do not want to replace parts of your protein with ions.

You could also use genion to add a specified concentration of ions in addition to simply neutralizing the system by specifying the -neutral and -conc options in conjunction. Refer to the genion man page for information on how to use these options.

The names of the ions specified with -pname and -nname are force field-specific. Refer to ions. You can safely delete this line, or leave it alone. Before we can begin dynamics, we must ensure that the system has no steric clashes or inappropriate geometry. The structure is relaxed through a process called energy minimization EM. The process for EM is much like the addition of ions.

We are once again going to use grompp to assemble the structure, topology, and simulation parameters into a binary input file. Assemble the binary input using grompp using this input parameter file: grompp -f minim. The -deffnm flag will define the file names of the input and output. So, if you did not name your grompp output "em.

In our case, we will get the following files:? The first is the potential energy printed at the end of the EM process, even without -v.

Epot should be negative, and for a simple protein in water on the order of , depending on the system size and number of water molecules. The second important feature is the maximum force, Fmax, the target for which was set in minim. If this happens, your system may not be stable enough for simulation.

Evaluate why it may be happening, and perhaps change your minimization parameters integrator, emstep, etc. Let's do a bit of analysis. The em. You can analyze any. You will be shown the average of Epot, and a file called "energy. To plot this data, you will need the Xmgrace plotting tool. To begin real dynamics, we the solvent and ions around the protein.

If we were to attempt unrestrained dynamics at this point, the system may collapse. It needs to be brought to the wish to simulate and establish the proper orientation about the solute the protein. After we arrive at the correct temperature kinetic energies , we will apply pressure to the system until it reaches the proper density. We're going to use it now.

The purpose of posre. Movement is permitted, but only after overcoming a substantial energy penalty. The utility of position restraints is that they allow us to equilibrate our solvent around our protein, without the added variable of structural changes in the protein.

Equilibration is often conducted in two phases. This ensemble is also referred to as "isothermal-isochoric" or "canonical.


Tutorials Overview

The solvated, electroneutral system is now assembled. Before we can begin dynamics, we must ensure that the system has no steric clashes or inappropriate geometry. The structure is relaxed through a process called energy minimization EM. The process for EM is much like the addition of ions. We are once again going to use grompp to assemble the structure, topology, and simulation parameters into a binary input file. Assemble the binary input using grompp using this input parameter file:.


Running molecular dynamics simulations using GROMACS

What is the correct procedure for performing a simple molecular dynamics simulation of a protein? Supporting Materials. It is often applied to large biomolecules such as proteins or nucleic acids. Multiple packages exist for performing MD simulations. For the tutorial, we will perform our simulations on hen egg white lysozyme. The trajectory is a binary file that records the atomic coordinates at multiple time steps, and therefore shows the dynamic motion of the molecule. Using visualization software, we can display this trajectory as a film displaying the molecular motion of the protein.



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