Molecular dynamics of a non-peptidic molecule with NAMD

1. Introduction
2. What's you need
3. Ibuprofen - water preparation
4. PSF file creation
5. NAMD minimization
6. Heating
7. Molecular dynamics
8. How to make resident the new parameter file

1. Introduction

This tutorial explains how to perform the molecular dynamics of the ibuprofen - water system with NAMD. The ibuprofen is a non-peptidic molecule and so some potential parameters are missing in the standard CHARMM 22 force field. TYou can learn how to fix the missing force field parameters and how to run NAMD without the VEGA ZZ graphic interface.

2. What you need

• VEGA ZZ release 2.0.8 or greater (click here for the software setup).
• NAMD for Windows (click here to download it). To install the NAMD package, follow this tutorial.

3. Ibuprofen - water preparation

• Start VEGA ZZ and select Edit Add Fragments. In the Add fragment/s window click Drug in the Group box and thus Ibuprofen in the Fragment box: in the workspace appears the 3D structure of the ibuprofen.
• Click Finish and the Close buttons.
• Deprotonate the carboxylic group selecting Edit Remove Atom in menu bar and clicking the hydrogen (see the red arrow):

The hydrogen is now deleted.

• To fix the bond order of the two oxygens of the carboxylate group (not requested by NAMD, but it's only a "cosmetic" problem), select Edit Change Bond: the Bonds window is shown. Choose One bond in What ? box and Partial double in Bond type box.
• Click the carbon and the oxygen as shown below:

The bond will be changed from double to partial double.

• Repeat the operation for the second C-O bond and finally click Done button.

• To remove the atom labels, select View Label atoms Off.
• Now the molecule will be inserted in a spherical water cluster. To do it, choose Edit Add Cluster menu item and the Cluster calculation window is opened.
• Choose the solvent type (WATER), the cluster type (Sphere in the Type box), set the sphere radius to 12.0 Å and click Ok button.
• Color the molecule by atom (View Color By atom).
• Fix the atom types and the charges (Calculate Charge & Pot.), checking Force field and Charges and selecting CHARMM22_PROT and Gasteiger.  The total charge is -1.
• Save the molecule in IFF format, naming the file ibuprofen_wat.iff (File Save As...).
• Save the molecule in PDB 2.2 format (ibuprofen_wat.pdb). This file is required by NAMD and it doesn't need the PDB connectivity and so you can avoid to save it unchecking Connectivity in the Options box.

4. PSF file creation

The ibuprofen doesn't have a standard topology and so the PSF file creation isn't totally automatic because some parameters aren't included in the CHARMM22_PROT parameter file. For more details about the input files required by NAMD, see this tutorial.

• Save the molecule in X-Plor PSF format (ibuprofen_wat.psf), selecting the force field name in the Force field param. box. The CHARMM22_PROT force field was used in the atom type attribution and so you must select the same force field. This operation is useful to check if all parameters needed by the ibuprofen are included in the force field parameter file.
• The Missing parameter table will be shown:

It indicates all angles, bonds and torsions parameters not included in the force field. In this window you can put manually the parameters, but if you don't know them, you can ask to the program to complete them for you.
Click Edit -> Auto assign and the table will be filled. Please remember that this isn't a full exaustive approach and it can generate wrong parameters. To check them, you can click on the missing parameter in the table and the involved atoms are automatically highlighted in the workspace.

• Filled the table, save the parameter file selecting File Save As... in the menu bar of the Missing parameter table window. Use ibuprofen_wat.inp as file name.
• Click the Ok button to save the PSF file and close the window.

5. NAMD minimization

Before to start the molecular dynamics simulation, an energy minimization is required.

• Copy in the directory where are placed the ibuprofen_wat.pdb, ibuprofen_wat.psf and ibuprofen_wat.inp files, the par_all22_prot.inp and par_all22_vega.inp parameter files that are in the ...\VEGA ZZ\Data\Parameters directory. The par_all22_vega.inp is required because VEGA ZZ generates a topology making explicit all improper angles.
• With a text editor (e.g. Notepad) create the input file with the following commands (copy & paste them):

numsteps                5000
minimization            on
dielectric              1.0

coordinates             ibuprofen_wat.pdb
outputname              ibuprofen_wat_min
outputEnergies          1000
binaryoutput            no
DCDFreq                 1000
restartFreq             1000

structure               ibuprofen_wat.psf
paraTypeCharmm          on
parameters              par_all22_prot.inp
parameters              par_all22_vega.inp
parameters              ibuprofen_wat.inp
exclude                 scaled1-4
1-4scaling              1.0
switching               on
switchdist              8.0
cutoff                  12.0
pairlistdist            13.5
margin                  0.0
stepspercycle           20

Save the file with the ibuprofen_wat_min.namd name. This performs a 5000 steps conjugate gradients minimization, saving the output (coordinates and restart files) every 1000 iterations. For more information about the parameters, please consult the NAMD User Guide.

• Open the VEGA console (Start VEGA ZZ VEGA console).
• Go to inside your working directory with the cd command.
• In the console, type:

namd2 ibuprofen_wat_min.namd > ibuprofen_wat_min.out

and hit return. After few time the minimization is finish.

• Select Calcualte Analysis and open the ibuprofen_wat_min.dcd trajectory file, clicking the open button.
• Click the Lowest button and save the lowest energy frame selecting File Save As... in the main window. Choose the PDB 2.2 format and ibuprofen_wat_min.pdb as file name.

6. Heating

This is the first molecular dynamics phase required to set the atom velocities at the specified temperature.

• In a text editor (e.g. Notepad), copy & paste the following commands:

numsteps		3000
dielectric              1.0

coordinates		ibuprofen_wat_min.pdb
temperature		0
seed			12345

outputname 		ibuprofen_wat_heat
outputEnergies  	1000
binaryoutput		yes
DCDFreq         	1000
restartFreq     	1000

timestep		1.0
nonbondedFreq   	1
fullElectFrequency 	1

structure               ibuprofen_wat.psf
paraTypeCharmm          on
parameters              par_all22_prot.inp
parameters              par_all22_vega.inp
parameters              ibuprofen_wat.inp
exclude			scaled1-4
1-4scaling		1.0
switching		on
switchdist		8.0
cutoff			12.0
pairlistdist		13.5
margin			0.0
stepspercycle   	20

langevin		on
langevinDamping		10
langevinTemp		300
langevinHydrogen	no

sphericalBC             on
sphericalBCCenter       0.0 0.0 0.0
sphericalBCr1           16.00
sphericalBCk1           2.00

• Save the file with ibuprofen_wat_heat.namd name. This input file performs a 0 to 300 K heating, using the Langevin algorythm and setting the spherical harmonic boundary conditions defining a virtual sphere of 16 Å radius, centered at the axis origin (0, 0, 0), using 2 as exponent of the boundary potential. These last parameters are required to reduce the solvent evaporation. For more information about the NAMD configuration, see the on-line documentation.
• Start the heating, typing in the console:

namd2 ibuprofen_wat_heat.namd > ibuprofen_wat_heat.out

and hit return.

7. Molecular dynamics

At the heating end, you must prepare the MD input file.

• In a text editor, copy & paste the following commands:

firsttimestep           3000
numsteps		103000
dielectric              1.0

coordinates		ibuprofen_wat_min.pdb
bincoordinates          ibuprofen_wat_heat.coor
binvelocities           ibuprofen_wat_heat.vel
extendedsystem          ibuprofen_wat_heat.xsc
seed			12345

outputname 		ibuprofen_wat_dyn
outputEnergies  	1000
binaryoutput		yes
DCDFreq         	1000
restartFreq     	1000

timestep		1.0
nonbondedFreq   	1
fullElectFrequency 	1

structure               ibuprofen_wat.psf
paraTypeCharmm          on
parameters              par_all22_prot.inp
parameters              par_all22_vega.inp
parameters              ibuprofen_wat.inp
exclude			scaled1-4
1-4scaling		1.0
switching		on
switchdist		8.0
cutoff			12.0
pairlistdist		13.5
margin			0.0
stepspercycle   	20

langevin		on
langevinDamping		10
langevinTemp		300
langevinHydrogen	no

sphericalBC             on
sphericalBCCenter       0.0 0.0 0.0
sphericalBCr1           16.00
sphericalBCk1           2.00

• Save the file with ibuprofen_wat_dyn.namd name. This input file performs a 100 ps molecular dynamics at 300 K constant temperature.
• To run the molecular dynamics, type:

namd2 ibuprofen_wat_dyn.namd > ibuprofen_wat_dyn.out

and hit return.

8. How to make resident the new parameter file

If you don't want reassign the parameters every time that you want perform the ibuprofen NAMD calculation, you can store them in VEGA ZZ.

• Copy the ibuprofen_wat.inp in the ...\VEGA ZZ\Data\Parameters directory.
• Open the ...\VEGA ZZ\Data\CHARM22_PROT.inp file with your preferred text editor:

*
* CHARMM 22 parameters file for VEGA ZZ
*
INCLUDE "Parameters/par_all22_lipid.inp"
INCLUDE "Parameters/par_all22_na.inp"
INCLUDE "Parameters/par_all22_prot.inp"
INCLUDE "Parameters/par_all22_vega.inp"
INCLUDE "Parameters/par_all22_user.inp"

• At the end of file, add the red line:

*
* CHARMM 22 parameters file for VEGA ZZ
*
INCLUDE "Parameters/par_all22_lipid.inp"
INCLUDE "Parameters/par_all22_na.inp"
INCLUDE "Parameters/par_all22_prot.inp"
INCLUDE "Parameters/par_all22_vega.inp"
INCLUDE "Parameters/par_all22_user.inp"
INCLUDE "Parameters/ibuprofen_wat.inp"

A better procedure, is to merge all user-defined parameters in the par_all22_user.inp that must be placed in the ...\VEGA ZZ\Data\Parameters directory. In this way, you mustn't edit the CHARMM22_PROT.inp file in the ...\VEGA ZZ\Data directory.

• In the VEGA ZZ console, type:

inpmerge "...\VEGA ZZ\Data\Parameters\par_all22_user.inp" "...\MyPath\ibuprofen_wat.inp"

where ...\VEGA ZZ is the VEGA ZZ installation path and the ...\MyPath is the full path of the ibuprofen_wat.inp file. For more information about the inpmerge utility, see its manual.

WARNING:
please remember that the INCLUDE command isn't implemented in NAMD and CHARMM, because they don't have a macro pre-processor. This is a feature available in VEGA ZZ only.