1. Molecular Dynamics Simulation

3. 1. Solvent + ion
To simulate aqueous
system, add water box
around the protein. The
solvated system
contains a charged
protein. Since life does
not exist at a net
charge, ions should be
added to neutralize the
system.
2. Energy
Minimization
Before starting
dynamics, one must
ensure that the system
has no inappropriate
geometry. Thus, the
structure is relaxed
through a process
called energy
minimization (EM).
3. NVT
equilibration
The solvent is mostly
optimized within itself,
and not necessarily
with the solute. It
needs to be brought to
the temperature one
wish to simulate and
establish the proper
orientation (based on
kinetic energies) about
the solute (the protein).
5. MD
Production
Upon completion of the
two equilibration
phases, the system is
now well-equilibrated
at the desired
temperature and
pressure.
The system is now
ready to run MDS for
data collection.
4. NPT
equilibration
Prior MD production,
one must also stabilize
the pressure (and thus
also the density) of the
system. Equilibration
of pressure is
conducted under an
NPT ensemble,
wherein the Number of
particles, Pressure, and
Temperature are all
constant.

4. Molecular Dynamics Simulation:
Lysozyme in a box of Water, with ions

5. Molecular Dynamics Simulation:
Lysozyme in a box of Water, with ions
● For this class, we will utilize hen egg white Lysozyme (PDB code 1AKI).
● Go to the RCSB website and download the PDB text for the crystal structure.
Click on “3D
Structure” View

6. Molecular Dynamics Simulation:
Lysozyme in a box of Water, with ions
Click on “Eye Icon”
besides Water option
to hide and show
water molecules.

7. Lysozyme in a box of Water, with ions:
1. Visit CHARMM-GUI: https://www.charmm-gui.org/ and
Sign-up. Click on “Solution Builder”
2. Provide PDB ID or Upload the file in the
a. “Protein Solution System” box.
3. Click on “Next Step: Select Model/Chain”
4. Check the appropriate protein chain and uncheck
Water to exclude water molecules attached to the
Structure.
5. Click on “Next Step:Manipulate PDB”
1. Solvent + ion
2. Energy
Minimization
3. NVT
equilibration
5. MD
Production
4. NPT
equilibration

8. 1. Solvent + ion
2. Energy
Minimization
3. NVT
equilibration
5. MD
Production
4. NPT
equilibration
Lysozyme in a box of Water, with ions:
1. Follow the manipulation option suggested by CHARMM-GUI unless
literature review suggests something different.
2. Click on “Next Step:Generate PDB”
3. Download “CHARMM PDB: step1_pdbreader.pdb” structure
4. Take a note of Ion Count to neutralize the system. (Click on “Calculate
solvent Composition” if you haven't found the information.)
5. Keep the other parameters as default.
6. Click on “Next Step: Solvate Molecule”
7. Check “Periodic Boundary Condition Options: Generate grid
information for PME FFT automatically” and Click on “Next: Setup
Periodic Boundary Condition”.

9. 1. Solvent + ion
2. Energy
Minimization
3. NVT
equilibration
5. MD
Production
4. NPT
equilibration
Lysozyme in a box of Water, with ions:
1. Select “GROMACS” under Input Generation Options.
2. Check “NPT Ensemble” under Dynamics Input Generation Options.
3. Click on “Next Step: Generate Equilibration and Dynamics inputs”

10. 1. Solvent + ion
2. Energy
Minimization
3. NVT
equilibration
5. MD
Production
4. NPT
equilibration
Lysozyme in a box of Water, with ions:
1. Download the input files clicking on “download.tgz” button.
2. Click on PBC Setup PDB “View Structure” to check the input structure.

11. Thank You