Simulation of

Density and RDF of H2O

Laboratory of Molecular Design and Materials Simulation

 Radial distribution functions

It is one of the easiest way to link a microscopic description of the system, to

macroscopic measurable quantities.
The function defines the deviation between the actual distribution of
molecules in space and a random distribution typical of the ideal gas.
It is given as the relative probability (calculated with respect to a random
distribution) to find two particles (atoms, molecules or larger entities) at a
distance r one from another. (This is actually the pair distribution function)
g(r)
Experimentally, it can be calculated (indirectly) from data of neutron
scattering or x ray scattering. The technique can be used to calculate
distribution fucntion for pairs of very small particles, down to the atomic
level; and this has been done in literature for a wide variety of systems..
Analyzing the quality of the structure obtained
 Water: a very special molecule
The simulation of liquid water usually requires special models, force fields and
parameters.
A water model is always the starting point for any force field development effort
toward a full description of biomolecular systems.
Biomolecular force fields are based on simple parametric energy functions, and
the quality of the force field parameters determines the reliability of the
computational results.
An ideal force field model of water should correctly reproduce the structural,
thermodynamic, and dynamic behavior of water.
However, due to its unique set of physical and chemical properties,
development of a water model based on a simple energy function that
accurately reproduces a wide range of water properties is still a
challenging task

Laboratory of Molecular Design and Materials Simulation

 Water models

Water models, derived from Quanto Mechanical calculations or from

experiments, are used to simulate liquid water, water solution and water
clusters absorbed in solids. Fake atoms with negative charge
representing the lone pairs of Oxygen
The water models can be classified by
(i) the number of interaction points (sites)

(ii) rigid or flexible bonds

(iii) with or without polarization effects. (polarizable models: If the polarity of the
environment increases, the dipole moment of water increases)
The model we use (TIP3P) is a popular rigid model using 3 sites, corresponding
to the 3 atoms of the water molecule. 3 sites models are computationally efficient
The geometry is fixed, as the model is rigid, and matches the actual geometry of
water molecules (angle of 104.5°).
 TIP3P model

Quantum and statistical mechanical studies of liquids. 10. Transferable

intermolecular potential functions for water, alcohols, and ethers. Application to liquid
water William L. Jorgensen J. Am. Chem. Soc., 1981, 103 (2), pp 335–340
 Polarizability of Water models

In TIP3P model, the energy function treats the nonbond terms in a pairwise
additive fashion and implicitly incorporates induced polarization by
optimizing the fixed partial atomic charges to yield average polarizable
induction in the bulk phase.
Such implicit treatment of has the inability to capture the sensitive polarizable
feature of water, and thus result in unbalanced descriptions among its
microscopic and bulk properties. For example, additive water models usually
overestimate the zero-field dipole moment in order to get better performance on
bulk properties.
To overcome this limitation, polarizable water models that explicitly treat the
polarization via different techniques including induced dipoles, fluctuating
charges, and the classical Drude oscillator (or Shell model), have been
developed in recent years
 TIP3P model for water in the CHARMM FF

TIP3P model for water is included in the more general Force Field CHARMM
which is used also to describe PROTEINS
 Water Force Field: CHARM

• The CHARM 22 protein (Chemistry at Harvard Macromolecular

Mechanics) is a popular force field for water.
• In the CHARMM22 protein force field, the atomic partial charges were
derived from quantum chemical calculations of the interactions
between model compounds and water. (MacKerell AD Jr; et al.
(1998). "All-atom empirical potential for molecular modeling and
dynamics studies of proteins". J Phys Chem B. 102 (18): 3586–
3616. doi:10.1021/jp973084f)
• CHARMM22 is parametrized for the TIP3P explicit water model.
 CHARMM for water and Proteins

The parameter evaluation was based on a self-consistent approach designed to

achieve a balance between the internal (bonding) and interaction (nonbonding) terms
of the force field and among the solvent−solvent, solvent−solute, and solute−solute
interactions. Optimization of the internal parameters used experimental gas-phase
geometries, vibrational spectra, and torsional energy surfaces supplemented with ab
initio results. The peptide backbone bonding parameters were optimized with respect
to data for N-methylacetamide and the alanine dipeptide. The interaction parameters,
particularly the atomic charges, were determined by fitting ab initio interaction
energies and geometries of complexes between water and model compounds that
represented the backbone and the various side chains. In addition, dipole moments,
experimental heats and free energies of vaporization, solvation and sublimation,
molecular volumes, and crystal pressures and structures were used in the
optimization. The resulting protein parameters were tested by applying them to
noncyclic tripeptide crystals, cyclic peptide crystals, and the proteins crambin, bovine
pancreatic trypsin inhibitor, and carbon monoxy myoglobin in vacuo and in crystals.
The presented parameters, in combination with the previously published CHARMM
all-atom parameters for nucleic acids and lipids, provide a consistent set for
condensed-phase simulations of a wide variety of molecules of biological interest.
 NOTE: Water models: TIP3P
In rigid models, bonding interactions are implicitly treated by constraints
between atoms coordinates due to the bonds.
The non bonded interactions are the electrostatic ones, represented by
Coulomb's law and the dispersion and repulsion forces represented by the
Lennard-Jones potential. The potential for models between two sites a and b in
model TIP3P is represented by
kC = electrostatic constant= 332.1 Å·kcal/mol;
qi = partial charges relative to electron charge;
rij = distance between two atoms or charged sites;
A, B = Lennard-Jones parameters.
Parameters for common 3-site water models
TIPS SPC TIP3P SPC/E
In most 3-site models, the Coulomb’s term
r(OH), Å 0.9572 1.0 0.9572 1.0
HOH, deg 104.52 109.47 104.52 109.47
applies to all atoms (O, H), while the LJ term
−3 12
A × 10 , kcal Å /mol 580.0 629.4 582.0 629.4 applies only to the interaction between the
B, kcal Å6/mol 525.0 625.5 595.0 625.5 oxygen atoms. So we say that the model has “a
q(O) −0.80 −0.82 −0.834 −0.8476 LJ site on the Oxygen and bare charge sites on
q(H) +0.40 +0.41 +0.417 +0.4238 the Hydrogens»

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 NOTE: Water models: TIP3P
COULOMB LENNARD JONES

The TIP3P model implemented in the CHARMM force field is a slightly

modified version of the original. The difference lies in the Lennard-Jones
parameters: unlike TIP3P, the CHARMM version of the model places
Lennard-Jones parameters on the hydrogen atoms too, in addition to
the one on oxygen. The charges are not modified.

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 Structural and dynamic properties of H2O

First you have to create a new project with a new

model (CTRL +N). Then rename the project
to MD_water and the model water.

Sketch in a water molecule. Change the building

atom in the toolbar to Oxygen, activate the Sketch
atom tool and sketch a single Oxygen atom in the
model window. Press ESC button to deactivate
theSketch atom tool, double click in the model
window to deselect the oxygen and press the Add
Hydrogen button in the toolbar. Your water molecule
is complete.

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 Assign force field to water

Assign Click on Assign force field icon located in

the Toolbar.
The Assign force field dialog appears.
From the Force field pull down menu select to assign
the CHARMm22_prot force field. Click on Apply.
CHARMM (Chemistry at HARvard Macromolecular
Mechanics)
In the CHARMM22 protein force field, the atomic partial
charges were derived from quantum chemical calculations of
the interactions between model compounds and
water.CHARMM22 is parametrized for the TIP3P explicit
water model.

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 Assign Force Field to water
In MAPS we have to assign the charges typical to
the TIP3P water model from Joergensen. (All other
parameters are automatically assigned by the force field file.)
Click on Manual tab in the Assign force field dialog.

In the model window select oxygen by

clicking on it. In the Force field
type select OT from the list and
set Charge to -0.834. Confirm by
clicking Apply. Double click in the model
window to deselect the oxygen and select Check the Atom type and the Force
field charge by labeling the
the two hydrogen atoms. Set the atom type molecule first with Atom type and
then with Force field charge. After
to HT and the Charge to 0.417. Confirm by you have confirmed that charges and
clicking OK (this closes the dialog as well). types are correct, set labeling
to None again.

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 Build the water box
Now we wish to build a periodic starting structure of our water. This will be done by
using the Amorphous Builder, located in Builders | Amorphous builder Open up
the Amorphous builder.
Note: that the project and model name appear in the build dialog.
Change Number to 100 and confirm by
hitting Return key, change the Density to 1.0 g/cm3. In
the Options tab click off Create new project. Leave all
other items at default values. Then click
the Build button. A note appears warning you about the
force-field truncation distance corresponding to this
system. Click OK to accept the suggested value
A new model in the same project appears,
called Amorphous model. Click Cancel in order to
close the Amorphous builder dialog.
Change the model name of the amorphous system
to waterbox and open the Model viewer on this model.
The model you get should look similar than the one
pictured.
431- 78648 Laboratory of Molecular Design and
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 Setting up the LAMMPS NVT-MD calculations

Next we will perform an NVT molecular dynamics simulation starting with the
periodic structure from the Amorphous builder.
In the Project manager select your model waterbox and right click on it. From within
the context menu select LAMMPS. When the LAMMPS interface appears,
change Name of Job to waterbox_nvt, in the Type of calculation pull down menu
of the General setup page select Molecular dynamics as type of calculation,
select the NVT ensemble from within the Ensemble pull down menu. Click Next.

In the Non bond interactions page leave everything at default and click Next.
In the Molecular dynamics page set Duration of run to 200 ps and leave everything
else at default, click Next.
In the Temperature control page leave all default parameters. Click on Next to
continue.
In the Output page set the Write trajectory file every to 1000 time steps.
Click Finish to submit the calculation.
A dialog box will appear and ask you if you want to start the calculation now. Click Yes.
You can view the progress of the calculation by using the Tools | Job manager. The
calculation should take approximately 1h on a single processor PC.
431- 78648 Laboratory of Molecular Design and
Materials Simulation
 Setting up the LAMMPS NVT-MD calculations

When the job is completed, a note appears on the screen informing you about the
completion of the calculation (see picture below)

Click Yes in order to upload the results. A new model, the results of the
molecular dynamics calculation called waterbox_nvt (output) is
automatically loaded and placed into the Result for waterbox_nvtresult in
the Project manager.
The upcoming Frames dialog (see below) enables you to load All or a
selected number of frames as well as load the velocities and calculate bonds
for each frame. In the present case you will load All frames and uncheck
the Calculate bonds option. Click OK.

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 Visualizing the results

If you visualize the result (select the results model in the Project manager, do a right
click and from the context menu select Model viewer if the viewer has not been opened
automatically) you will see bonds through the cell from one side to the other.
These bonds are a result of the periodic boundary conditions (a water molecule has
atoms on both sides of the box) and can be corrected by pressing the Calculate
bonds button from the Tool bar.
For the time being, leave the system as it is.

The evolution of the total energy and its

components can be viewed by clicking on
the Show trajectory graph button in
the Toolbar.
The dramatic drop in energy at the
beginning of the simulation, when the
close contacts introduced in the
building process by the Amorphous
builder are removed.

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 Analyzing the quality of the structure obtained

This can be done for instance by calculating the Oxygen-Oxygen Radial Distribution
Function (RDF) of the output structure. In order to calculate this functions, first change
the selection mode to Element through the Choose selection mode pull down
menu in the Toolbar and select all oxygens in your structure by clicking on
one oxygen in the model window.
Then click on the Trajectory analysis button in the Tool bar. Go in the Structure tab
and select Radial distribution function, leave everything else at default and
click Apply. The result should look like that depicted in the picture below..
Oxygen-Oxygen Radial distribution function
EXPERIMENTAL
Compare with
SIMULATED
experimental data
for RDF of O-O of
water: GOOD
MATCH!

431- 78648 Laboratory of Molecular Design and

Materials Simulation
Analyzing the quality of the structure obtained
 Calculate density with an NPT MD run

Now we finally check if we can predict the density of our water system correctly.
In order to do so, we will run an NPT simulation with LAMMPS. Open the Model viewer
on the model waterbox_nvt (output). We will start from the last configuration of the
NVT run and need to make sure that the structure which corresponds to the results
model is the last obtained at the previous MD run.
In order to do this deploy the Conformations level and click to select the last one.
Then reduce the waterbox_nvt (output) tree. Now first select, then right click on your
model waterbox_nvt (output) and select LAMMPS.
In the General setup page change the Name of job to waterbox_npt and
select Molecular dynamics and NPT in the Type of calculation and Ensemble pull
down menus. Click Next.
In the Non bond interactions page leave everything at default and click next, in
the Molecular dynamics page set Duration of run to 50 ps and leave everything else
at default, click Next.
In the Temperature control page leave all default parameters. Click on Next to
continue. Do the same in the Pressure control page and click Next. In the Output page
set the Write trajectory file everyto 500 time steps. Click on Finish to submit the
calculation. A dialog box will appear and ask you if you want to start the calculation now.
Click Yes
 Calculate density with an NPT MD run

.
You can view the progress of the calculation by using the Tools | Job manager. The
calculation should take approximately 15 minutes on a single processor PC.
When the job is completed, a new model, the result of the molecular dynamics
calculation called waterbox_npt (output) is automatically loaded. Click OK in the
upcoming Frames dialog box to load every frame. If you visualize the result (select the
results model in the Project manager, right click and from the context menu select Model
viewer) you will again see bonds through the cell from one side to the other. Correct this
by pressing the Calculate bonds button from the Tool bar. You will see these bonds
disappear. You can now animate the trajectory by clicking on the Animate
trajectory button in the Toolbar. You can stop the animation by clicking the Stop
animation button .
To check the density of the system open up the model waterbox_npt (output) in
the Project manager. Select the Unit cell item, and right click it. Select View unit cell
properties. In the upcoming property list at the bottom of your window, note the density.
It should be 1.018 g/cm3.

431- 78648 Laboratory of Molecular Design and

Materials Simulation
 Example: build a cyclo-C6 molecule

1) Create a new project with a new model through File | New | New atomistic project + model or
with the shortcut CTRL +N. An Unnamed project and an Unnamed model appear in the Project
manager. Select Rename project and type in mixture. Click now on the model, select Rename
model. Type in Cyclohexane.

2) Sketch in the cycloC6 molecule. Activate the Sketch atom tool and sketch a 6 member ring of C
atoms in the model window. Press ESC button to deactivate the Sketch atom tool, double click in the
model window to deselect the last sketched atom and press the Add hydrogen button in the Toolbar.
Your molecule is complete.

3) Assign a force field to the system. Click on Assign force field button in the Toolbar. The Assign
force field dialog appears. In the first tab you will select the force field: Select Amber_Cornell.
Click OK.
4) Optimize the structure using MAPS' Optimizer engine. Therefore, go to the Project manager,
select the model cylohexane and right click to open the menu. Select Optimizer. The Optimizer
dialog appears. Click on Use threads, set Steps to 1000 and leave everything else at default.
Click OK to optimize the structure. Once the optimization has finished click on Cancel to close the
dialog. Now you should observe the typical Cyclohexane chair structure.
Example: build a cyclo-C6 molecule