heromdanalysis: an automagical tool for gromacs based ......selection screen for radius of gyration...

HeroMDAnalysis An Automagical tool for GROMACS based Molecular

Dynamics Simulation Analysis

HeroMDAnalysis Step by Step Installation Guide

Please read the instructions given to install the tool You may also visit the video tutorial

provided here httpswwwyoutubecomwatchv=GGOmwzGWaSk

A) Step by Step Installation Guide (For Linux Machine)

Step 1 The user should be running a linux operating system The program is successfully

tested on Ubuntu and BOSS linux system But practically the tool should work on any linux

environment

Step 2 The user should have GROMACS 20194 or higher installed on your linux machine

Please visit GROMACS website httpwwwgromacsorg to know how to install GROMACS

Step 3 The user should have Xmgrace installed on your linux system If you want install

Xmgrace on debian based systems like Ubuntu and BOSS linux You can do it using terminal

by the following command sudo apt-get install grace and to install Xmgrace for other

distributions you may visit this website httpplasma-gateweizmannacilGrace

Step 4 The new version of the tool requires SHC Shell Compiler installed Use the following

commands to install SHC Shell Compiler on your linux machine First sudo add-apt-

repository ppaneurobinppa and second sudo apt-get update and then sudo

apt-get install shc

Step 5 After obtaining a copy of program extract the zip file in the folder where xtc edr and

tpr files of Molecular Dynamic simulation are placed and using terminal type following two

commands First chmod +x launchsh and finally launchsh to launch the tool

B) Step by Step Installation Guide (For Windows Machine with Linux Subsystem)

Step 1 The user should be running a windows operating system The program is successfully

tested on Windows 10 Then use the following tutorial to install linux subsystem on windows

httpswindowsloopcominstall-linux-subsystem-windows-10

Step 2 Install Xming on the windows machine by downloading the setup file from this website

httpssourceforgenetprojectsxming Then launch Xming and allow network access when

prompted through firewall application

Step 3 Install Zip and Unzip on the linux subsystem using the following commands For Zip

sudo apt-get install zip and for Unzip sudo apt-get install unzip

Step 4 Install Zenity on the linux subsystem using the following commands First sudo apt-

get update -y and then sudo apt-get install -y zenity

Step 5 The user should have GROMACS 20194 or higher installed on the linux subsystem


Step 6 The user should have Xmgrace installed on your linux system Please install it by the

following command sudo apt-get install -y grace




apt-get install shc



commands First chmod +x launchsh and finally DISPLAY=0 launchsh to launch

the tool

User manual

Module 1

The Program launch screen shows the program version list of developers

information regarding the tool website httpsheromdanalysiswordpresscom to visit for

more information and the terms and conditions user has to agree and accept before using this

tool Press Accept button to proceed further

Then comes the User authentication screen to authenticate the login and usage of the

tool The credentials for this screen must be obtained by filling the registration form available

at the website httpsheromdanalysiswordpresscomcontact-us

This is the dialog to remind the user for the availability of three files namely

md_0_10tpr md_0_10edr and md_0_10xtc or md_0_10_fitxtc in the present working

directory of the tool Also the files generated would be organized and saved in this directory

Press Proceed button

The selection window requires user to choose the system of analysis The available

options are a) Protein-ligand Complex or b) Apoprotein The options differ in the format that

there are ligand parameters available in the list of Protein-ligand complex while these are

absent in Apoprotein The user has to select one option for analysis and press the Select button

Selection menus for available parameters

In common theses screens would display list of available option for single or multiple

entries User may tick specific or all options and press Select button to proceed further If no

option is desired then press Skip button

Selection screen for Root-mean-square-deviation

The graph is plotted for RMSD value (nanometer) on y axis vs Time (nanosecond) on

x axis

The list contains various options namely

A) Calpha-PL Backbone-PL Sidechain-PL and Protein-PL These options will

calculate RMSD value for protein-ligand complex (PL) and prefix terms denotes the

selection of atoms for the calculation of RMSD For example in Calpha-PL the RMSD

will be calculated by overlapping the Calpha atoms over the series of frames of

trajectory file

B) RMSD-L Lig fit Prot and Prot fit Lig are some other RMSD terms involving the

selection of ligand atoms one way or the other for the calculation for RMSD values for

the trajectory More information about these terms can be obtained from gromacs

website (wwwgromacsorg)

Selection screen for Root-mean-square-fluctuation

The graph is plotted for RMSF value (nanometer) on y axis vs Time (nanosecond) on

x axis



calculate RMSF value for protein-ligand complex (PL) and prefix terms denotes the

selection of atoms for the calculation of RMSF For example in Calpha-PL the RMSF

will be calculated by analyzing the fluctuation for Calpha atoms over the series of

frames of trajectory file

B) RMSF-L is RMSF term involving the selection of ligand atoms and then calculating

the fluctuation over the series of frames of the trajectory More information about these

terms can be obtained from gromacs website (wwwgromacsorg)

Selection screen for Radius of gyration

The graph is plotted for Rg value (nanometer) on y axis vs Time (picosecond) on x axis


A) Calpha-PL Backbone-PL Sidechain-PL and Protein-PL These options will study

the compactness of the protein-ligand complex (PL) and prefix terms denotes the

selection of atoms for the calculation of RoG For example in Calpha-PL the RoG will

be calculated by analyzing the distribution of Calpha atoms around the imaginary axis

of protein over the series of frames of trajectory file

B) RMSF-L is RoG term involving the selection of ligand atoms and then calculating the

compactness of ligand atoms over the series of frames of the trajectory More

information about these terms can be obtained from gromacs website

(wwwgromacsorg)

Selection screen for Solvent accessible surface area

The graph is plotted for area value (nanometer2) on y axis vs Time (picosecond) on x

axis

The list contains the options namely

A) Protein Residue or Atomic SASA to calculate solvent accessible surface area (y axis)

for each residue or atom in the ensemble (x axis) respectively The image generation is

only supported for the Protein-Residue SASA plot Please select this option to obtain a

plot SASA vs Residue number for protein

B) Ligand Fragment or Atomic SASA to calculate solvent accessible surface area (y

axis) for fragments or each atom in the ensemble (x axis) respectively The image

generation is only supported for the Ligand-Fragment SASA plot Please select this

option to obtain a plot SASA vs Fragment for ligand More information about these


Selection screen for Free energy of solvation

The graph is plotted for change in Gibbrsquos free energy (kJmol) on y axis vs Time

(nanosecond) on x axis


A) Protein Free energy of solvation This selection will calculate change in Gibbrsquos free

energy solvation term for protein

B) Ligand Free energy of solvation This selection will calculate change in Gibbrsquos free

energy solvation term for ligand For more information about these terms please visit

gromacs website (wwwgromacsorg)

Selection screen for H-bond contact analysis

The graph is plotted for number of H-bond contacts on y axis vs Time (nanosecond) on

x axis


A) Ligand-Protein H-bonds This option calculates the number of H-bond contacts

between ligand and protein for the complete duration of simulation

B) Intra-Protein H-bonds This option calculates the number of H-bond contacts

between among protein residues for the complete duration of simulation

C) Protein-Water H-bonds This option calculates the number of H-bond contacts

between protein and water molecules for the complete duration of simulation

Selection screen for H-bond contact analysis of various thermodynamic parameters


A) Temperature The graphs is plotted between temperature (kelvin) on y axis vs time

(picosecond) on x axis for complete duration of simulation trajectory

B) Pressure The graphs is plotted between pressure (bar) on y axis vs time (picosecond)

on x axis for complete duration of simulation trajectory

C) Potential The graphs is plotted between potential (kJmol-1e-1) on y axis vs time


D) Density The graphs is plotted between density (kgm3) on y axis vs time (picosecond)


E) Total Energy The graphs is plotted between total energy (kJmol) on y axis vs time


Selection screen for H-bond contact analysis of Principle component analysis

The raw data for these parameters is analysed and extracted The image processing for

these paramters is not done However the raw data obtained can be used and subjected to

Xmgrace and plots can be generated manually


A) Covariance analysis for Backbone and Calpha

B) AnaEig analysis for Backbone and Calpha

C) 1D Eigenvec analysis for Backbone and Calpha

D) 2D Eigenvec analysis for Backbone and Calpha

E) RMSF Eigenvec analysis for Backbone and Calpha

Analysis of Parameters

The dialog for launching of selected jobs Press OK button to proceed Allow the tool

to work in the background All the data will be generated automatically and will be organized

in folders This will appear with lot of things happening in the folder Please donrsquot interfere

with any file being generated in this folder Other parallel tasks on the computer wonrsquot be

interfere

The progress bar displays progress level and text displays parameter name under current

progress Kindly wait for ldquoFinishedrdquo text to appear Until then donrsquot press any button

The job completion dialog which shows completed progress bar and ldquoFinishedrdquo

notified The tool now await confirmation by pressing OK button to proceed further

Plotting to High quality images

The selection window requires user to choose to plot images The available options are

a) Yes letrsquos plot data to HD quality images or b) No I donrsquot want it By selecting option a)

the raw data generated from the previous step would be plotted to HD quality images that can

be used for visualization and publication The option b) exits the tool here with the raw data

generated in previous step in an organized manner This data is always available for the user

and can be used to plot graphs using Xmgrace MS Excel or other plotting tools The user has

to select one option and press the OK button

If the user selected option b) the tools exits with the screen listing authors and other

information about the tool

If the user selects option a) then a notification for the beginning of plotting raw files to

HD quality image files appears And the user is prompted to provide some required information

on the subsequent steps

Prompt windows for required text to be placed on title of image files and axis information

required for plotting

1 PDB ID of the protein It is the 4-digit alpha-numeric code Please enter the required value

here For example 4PD4 Press OK button to proceed

2 Name of the ligand It is the name of the ligand that user wants to provide Please provide

name in the form of alphabets and numeric Kindly donrsquot use brackets and spaces in this

column For example C008234 Press OK button to proceed

3 Duration of the molecular dynamic simulation The unit for this value is in nanoseconds

For example for 100ns simulation the entry value is 100 Press OK button to proceed

Progress bar for plotting of selected parameters to image plots and text showing current

parameter under progress And notification for the user-interactive plotting of calpha_rmsd

plot Here user is asked to provide desired values in an entry box with Xmgrace window

opened in adjacent for reference

A screen with Xmgrace window on the left showing the calpha_rmsdxvg plot and entry

box on right awaiting user to enter the max value of y axis which can be 03 or other as required

by the user for the plot appearance

Similar screen with Xmgrace window on left showing calpha_rmsdxvg plot and entry

box on right awaiting user to enter the minor tick value of y axis which can be 005 or other as

required by the user for the appearance

A notification for the user-interactive plotting of calpha_rmsf plot Here the user is

asked to provide desired values to be filled in an entry box with Xmgrace window opened in

adjacent for reference Press OK button to proceed further

A screen with Xmgrace window on left showing the calpha_rmsfxvg plot and entry

box on right awaiting user to enter the max value of x axis The user has to point at the right

end of curve using mouse to read numeric value shown in the bar under the menus bar at the

top For example in this case the value was found to be 998 Press OK button to proceed

further

Similarly the entry box on right await user input for min value of x axis Again the

user has to point at left end of the curve using mouse cursor and read value shown in the bar

under the menus bar at the top For example in this plot the value was found to be 670 Press

OK button to proceed further

Similarly the entry box on right await user input for minor tick value of x axis Here

the user can look at the x axis at bottom to decide a suitable tick value For example in this

plot the value 25 was found to be optimum Press OK button to proceed further


progress Please wait for the progression of the work

A similar set of steps are required for plotting the ligand_rmsdxvg data as done for

calpha_rmsdxvg

A similar set of steps are required for plotting the ligand_rmsfxvg data as done for

calpha_rmsfxvg


progress Please wait for the progression of the work The upcoming data doesnrsquot require user

interactive plotting instead it progress with automation

Screen for the successful completion of the plotting task Press OK button to proceed

further

An exit screen display information regarding name of developers and tool after

successfully completing assigned analysis and plotting tasks Press OK to exit

Module 2

The Program launch screen shows the program version module version information

regarding the tool website httpsheromdanalysiswordpresscom to visit for more

information and the terms and conditions user has to agree and accept before using this tool

Press Accept button to proceed further [Note The terminal window in the background should

be kept in this case of module II because module II takes user input for various steps through

the terminal]






The screen display list of available option for selection of single or multiple entries In

common all these parameters require an index file The first option being ldquoMake indexndx

filerdquo User may tick specific or all options and press Select button to proceed further If no



1 Making Indexndx file

The program notifies for the parameter under progress and the user have to use

the terminal to select different point(s) for creating index file

The format for specifying any coordinate should be as

1) For a complete molecule (for example protein) 1

2) For a residue of the protein (for example residue 864) 1 amp r 864

3) For a specific atom of the protein (for example atom 1788 of residue 850) 1 amp r

850 amp a 1788

Likewise single or multiple entries can be created

After specifying various points the user may use the pipe function to merge different

entries created into one in case multiple points have been created For example here entries

22 and 23 are getting merged using 22 | 23 function

The terminal would display the groups have been merged and a new merged entry have

been created

After successful creation of the entries in index file for various parameters like for

computing distance (at least two points must be specified) for computing angle (at least three

points must be specified) The user can end with typing q and hitting enter

The next screen asks the user to supply the name to save the index file

Here the user may specify the name and hit OK button [Note It is always better to

save the index file with coordinate information so any confusion in future could be avoided]

2 Compute Distance

For computing distance the program notifies the user to select the index file in which

two points have been specified for which the distance has to be calculated

The file selection dialog for the index file for computing distance The user here can

select the particular index file and hit OK button

The next screen asks the user to supply the name to save the distance plot xvg file


save the plot file with its coordinate information so any confusion in future could be avoided]

Now the distance computation will begin the program asks the user to specify the

positional pairs using the terminal

After carefully selecting the specific entry the user may press ctrl + D to begin the

calculations The raw data and image plots are saved in respected directories

3 Compute Angle

For computing angle the program notifies the user to select the index file in which three

points have been specified for which the angle has to be calculated

The file selection dialog for the index file for computing angle The user here can select

the particular index file and hit OK button

The next screen asks the user to supply the name to save the angle plot xvg file


save the plot file with its coordinate information so as to avoid any confusion in future]

Now the angle computation will begin the program asks the user to specify the entry

for the three-atom pair using the terminal

The raw data and image plots are saved in respected directories

4 Compute Dihedral (Ramachandran Plot)

This calculation is done automatically and no user input is required in this case The

raw data and image plots are saved in respected directories

5 Compute Dihedral (per residue)

For computing dihedral on per residue basis the program notifies the user to specify

the particular residue

The residue selection dialog for computing dihedral on per residue basis The format

for specifying any residue should be as

1) For a residue (for example residue type Glycine at residue number 700) GLY-700


6 Cluster structures

For clustering structures the program notifies the user to select the group for least

square fit and RMSD calculations

Using the terminal the user may specify the group for least square fit and RMSD

calculations For example if the C-alpha atoms are to be selected the user have to type 3 and

press enter

7 Compute RMSD using indexndx

For computing RMSD using indexndx the program notifies the user to select the index

file in which three or more points have been specified for which the Root-Mean-Square-

Deviation has to be calculated

The file selection dialog for the index file for computing RMSD The user here can


The next screen asks the user to supply the name to save the rmsd plot xvg file Then

the user may specify the name and hit OK button [Note It is always better to save the plot file

with its coordinate information so any confusion in future could be avoided]

Now the RMSD computation will begin the program asks the user to specify the index

group for least square fit using the terminal

After carefully selecting the specific entry the user may press enter to begin the


8 Compute RMSF using indexndx

For computing RMSF using indexndx the program notifies the user to select the index file

with the specific points for which the Root-Mean-Square-Fluctuation has to be calculated

Now the RMSF computation will begin the program asks the user to specify the index

group for root-mean-square calculation



9 Compute ROG using indexndx

For computing ROG using indexndx the program notifies the user to select the index

file with the specific points for which the radius of gyration has to be calculated The next

screen asks the user to supply the name to save the rog plot xvg file



Now the radius of gyration calculation will begin the program asks the user to specify

the entry using the terminal

After successful completion of all the tasks An exit screen would display information

regarding module and tool Press OK to exit

Step 3 Install Zip and Unzip on the linux subsystem using the following commands For Zip

sudo apt-get install zip and for Unzip sudo apt-get install unzip

Step 4 Install Zenity on the linux subsystem using the following commands First sudo apt-

get update -y and then sudo apt-get install -y zenity

Step 5 The user should have GROMACS 20194 or higher installed on the linux subsystem


Step 6 The user should have Xmgrace installed on your linux system Please install it by the

following command sudo apt-get install -y grace




apt-get install shc



commands First chmod +x launchsh and finally DISPLAY=0 launchsh to launch

the tool

User manual

Module 1

The Program launch screen shows the program version list of developers

information regarding the tool website httpsheromdanalysiswordpresscom to visit for

more information and the terms and conditions user has to agree and accept before using this

tool Press Accept button to proceed further


















x axis






trajectory file







x axis





















(wwwgromacsorg)



axis






















x axis



































interfere












































further











calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter
















































x axis






trajectory file







x axis





















(wwwgromacsorg)



axis






















x axis



































interfere












































further











calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter



































x axis





















(wwwgromacsorg)



axis






















x axis



































interfere












































further











calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter










































(wwwgromacsorg)



axis






















x axis



































interfere












































further











calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter













































x axis



































interfere












































further











calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter
































































interfere












































further











calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter








































































further











calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter









































calpha_rmsdxvg


calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter
































calpha_rmsfxvg





further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter



































further



Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter































Module 2






the terminal]


















850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter












































850 amp a 1788






been created







2 Compute Distance












3 Compute Angle


























press enter




































been created







2 Compute Distance












3 Compute Angle


























press enter





































2 Compute Distance












3 Compute Angle


























press enter






































3 Compute Angle


























press enter



















































press enter































heromdanalysis: an automagical tool for gromacs based ......selection screen for radius of gyration...

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