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Introduction to Hydrolab

1.1 Overview of Molecular Lab

Molecular Lab is a free molecular dynamics simulation tool that part of the nanoHUB project, which is spearheaded by Network for Computational Nanotechnology (NCN). The tool is available on the nanoHUB website, [www.nanohub.org].

The biggest advantage of Molecular Lab is its simplicity. Molcular Lab is provides a user-friendly graphical user interface, where the user can simulate molecular interactions of any molecules with water by using an advanced molecular dynamics simulation software. The following instructions explain the basic information the usern needs, in order to have a better understanding of the inner workings of the software on which this program is based.

Molecular Lab allows the user to input any molecule written in the PDB (Protein Data Bank) format. PDB format is a file format specified by Protein Data Bank (http://www.rcsb.org/pdb/home/home.do). PDB format specifies the types of atoms and their positions in x, y and z co-ordinates. PDB files of various molecules can be viewed and downloaded from the PDB website. In this software, you will be able to tune the interaction between water and molecules of any type.

Calculations of the actual molecular dynamics simulation are performed by simulation software called GROMACS. Capabilities of the software can be seen on the GROMACS website, [www.GROmacs.org]. GROMACS takes various input files in different formats, but Molecular Lab simplifies the entire simulation process into a friendly Graphical User Interface (GUI). By following each step in the top tabs of the GUI, the user can upload files and input various parameters without ever having to deal with the complex process of MD simulation of GROMACS.

2.1 Program Inputs Description

Molecular Lab follows the basic Molecular Dynamics simulation process of GROMACS, a MD simulation program. There are some main file types involved in a standard GROMACS simulation process. There are detailed explanations of these file types on the GROMACS website. (http://www.gromacs.org/external/online-reference-manual.html).

Here is a list and brief explanations of important file types involved in Molecular Lab

PDB file: Protein Data Bank (PDB) file is the first input file format for the first stage of the MD simulation process. PDB file contains information about the types of atoms and their positions in the input molecule. Output files are created based on the content of the PDB file.

GRO file: GRO file format is a structure file format very similar to the PDB file format. This is the format of the file that is created after the molecule written in the PDB format is mixed with water. GRO file can also include the velocities of each atom in x, y and z directions.

TOP file: TOP is a topology file format that includes information about the number of solvent and water molecules and bond parameters. TOP file is created after the molecule is mixed with water.

MDP file: MDP is a dynamic file format that includes information about all essential bonding parameters and other information pertinent to mdrun simulation step. The user is able to specify maximum bond angles and other information that determines the accuracy of the simulation.

TRR file: TRR is a trajectory file format that includes information about the final mdrun simulation step recorded every pre-specified time step. TRR file can be downloaded and input into visualization tools like Pymol to view the simulation process.

The following flowchart represents the overall MD simulation process with Molecular Lab.

Although the actual simulation steps involved in the GROMACS simulation include many steps, Molecular Lab has simplified the entire simulation process into 5 simple steps. There are only 3 different patterns where the user inputs files to Molecular Lab. As described in the flowchart, in Pattern 1, the user has the input PDB file where the molecule is yet to be mixed with water. In Pattern 2, the user already has GRO and TOP files and uploads them onto Molecular Lab. In this situation, the simulation starts from the energy minimization process instead of solvate process, since GRO and TOP files are products of the solvate process. In Pattern 3, the user already has the final TRR file before the final mdrun. In this case, Molecular Lab only goes through the final mdrun without restraints. As mentioned earlier, Molecular Lab consists of 5 phases. Here is a list of explanations for each step.

1. PDB and MDP The user is asked to choose the situation that applies to them from having only PDB file, having TOP and GRO files, and having TPR file for the final mdrun. Depending on the choice, certain inputs are blocked in other phases, so that the user can easily recognize what files need to be uploaded. In addition, the user is able to upload their PDB or gro file on this phase. When the user tries to upload a file onto Molecular Lab, a pop-up window like the following appears.

On the bottom of the window, there is a yes/no question asking whether the user wants to go through the position restrained mdrun process. For MDP files, the user has the option of either uploading the file or filling a form, from which an MDP is automatically created.

2. Box generation and energy minimization In this phase, the user is asked to specify various parameters for the energy minimization process. Depending on whether the user has a TOP file or not, a window to upload a TOP file is activated or not. Otherwise, the user is able to choose from a list of force fields.

3. MDP file parameters If the user answered that they have no MDP file in the phase 1, the user is able to input MDP parameters in this phase. The parameters are divided into different sections such as electrostatics and output control. The user’s inputs are directly substituted into an MDP file, which is used in the position restrained and final production run.

4. Preprocessing run The user chooses whether they wish to have the final production run. If the user chooses no, the simulation stops right before the production run and when successful returns a message of success. If the user chose in phase 1 that they have a TPR file for the final mdrun, the user is able to upload their TPR file at this point. This is an essential step before the final production run that minimizes the energy of the system.

6. Simulate As soon as the user clicks the simulate button, the simulation automatically starts. This includes all the pre-processing steps or, if selected, the production run. When successful, all the output files from various stages of the simulation are displayed for download. The user is also able to view the 3D graphics of the starting and final molecular configurations.

3.1 Program Outputs Description

After the final mdrun without restraints is done, Molecular Lab allows the user to download several different files. The tool allows the user to download the output GRO, TOP, MDP and TRR files. In addition to the file downloads, the tool also visualizes the input and output molecule in a small screen. To get a more detailed dynamic visual output, the user has to download the TRR file and input the file into a visualization tool such as Pymol. Below is Hepatitis C Virus visualized by Real VMD. As explained earlier, TRR file includes information about the dynamics of the molecule inside water, so the by using visualization programs, the user is able to see how molecules interact with water from various different angles. Other files such as GRO and TOP can be downloaded so that they can be reused when the user wants to repeat the same reaction but with different MDP parameters. This way, the user does not have to start from scratch and can save some time by skipping the solvate step.

Hydrolab generates several different types of output files such as:

  1. Lennard-Jones potential plots
  1. Initial and final configuration images
  1. Trajectory file in a PDB format
  1. Log file of the simulation run

These files can be saved either by using the download button next to the scroll down icon or scroll down and click "download".

4.1 Practice Examples

Example 1 Hepatitis C Virus

  1. Download the PDB file of hepatitis C virus from http://www.rcsb.org/pdb/explore.do?structureId=1R7E.
  1. Upload this PDB file in the first step.
  1. In the third step of entering mdp file parameters, enter the following values.
Run and Output Control
Choose an IntegratorMolcular Dynamics
Center of mass optionsLinear
Neighbor Search
Search Algorithmgrid
Periodic boundary conditionsxyz
Electrostatics and Van der Waals
Algorithms to compute Coulomb forcesCut-off
Van der Waals potentialCut-off
Choose a display optionno
Ewald options
Geometry for the Ewald summations3D
Optimize FFTsno
Temeperature/Pressure?
Choose the temperature coupling typeno
GroupsATOMS
Pressure coupling optionsNo pressure coupling
Velocity Generation
Generate velocity?no
Bond parameters
Choose the bond constraint typeno
Choose the constraint algorithmlincs
Choose Yes for an unconstrained startno
Choose Yes to user a Morse potential instead of an harmonic potentialno
  1. Download the output .trr file and input it into a graphics program like VND or Pymol. The following is an post-simulation image created by VMD.

5.1 Contributors

Contributor NamenanoHUB login or other contact information
Eric Darvedarve Stanford University
Kazutora Hayashidahayaska Stanford University