10 Applications of Molecular Dynamics Simulations …
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2. Prepare the protein structure using the Protein Preparation Wizard from Maestro.
Ions and other small molecules are removed, bond orders are corrected, and the
missing residues, atoms, and hydrogens are added to the system. Lastly, reliable
protonation states of the residues are set.
3. Generate a solvated system using a Solvation tab. This step adds water molecules
around a protein or inserts a protein into a lipid layer. The Solvation tab has the
following options: (a) none—Do not use the solvent (run the system in a vacuum);
(b) predefined—Select one of the solvent models such as SPC, TIP4P, TIP3P, and
TIP4PEW and three organic solvents, methanol, octanol, and dimethyl sulfoxide
(DMSO); (c) custom—Import the solvent system from a file. The Solvation tab
also sets up the periodic boundary box by specifying the shape and size of the
box. To proceed with this step, first select the shape of the box from the three
basic shapes: cubic, orthorhombic, and triclinic. While selecting, the box size
calculation has two options: (i) buffer—Calculate the size using the given buffer
distance between the solute and the box boundary and (ii) absolute size—Specify
the distance between the solute and the simulation box.
4. Insert the protein into a lipid layer with the setup membrane from system builder
panel if the target system is a membrane protein. DPPC, POPC, and POPE are
the three membrane models supported by Desmond.
5. Calculate the charge of the system. Positive (Na
+ ) or negative (Cl
− ) ions are
added to neutralize the solvated system or to set a desired ionic environment for
the protein.
6. Before MD simulations, relax the whole system into a local energy minimum
either by minimization or by selecting the panel options. In this step, the system is
minimized by the steepest descent method followed by limited-memory BroydenFletcher-Goldfarb-Shanno (LBFGS) algorithms. Generally, two parameters are
set for the minimization: (i) maximum number of iterations and (ii) convergence
threshold for the gradient.
7. Utilize the desmond panel to set the simulation parameters such as production
run, simulated annealing, or replica exchange for the system. The simulation
section is where the user specifies the simulation time (in nanosecond) and the
recording time interval (in picosecond) for the energy calculation and between
the snapshots in the trajectory file. Additionally, selecting the ensemble type
(such as NVT, NPT, NVE, NPγT, and NPAT) to set the temperature, pressure,
and surface tension occurs in the simulation Section.
8. Finally, run the simulation. The resultant trajectory is analyzed by the simulation
quality analysis or the simulation event analysis panel. The result includes a
summary of the simulation and analysis of total and potential energy, temperature,
pressure, and volume throughout the simulation.
10.5 MD Simulation Protocol
An overview of the MD simulation protocol is depicted in Fig. 10.5.
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2. Prepare the protein structure using the Protein Preparation Wizard from Maestro.
Ions and other small molecules are removed, bond orders are corrected, and the
missing residues, atoms, and hydrogens are added to the system. Lastly, reliable
protonation states of the residues are set.
3. Generate a solvated system using a Solvation tab. This step adds water molecules
around a protein or inserts a protein into a lipid layer. The Solvation tab has the
following options: (a) none—Do not use the solvent (run the system in a vacuum);
(b) predefined—Select one of the solvent models such as SPC, TIP4P, TIP3P, and
TIP4PEW and three organic solvents, methanol, octanol, and dimethyl sulfoxide
(DMSO); (c) custom—Import the solvent system from a file. The Solvation tab
also sets up the periodic boundary box by specifying the shape and size of the
box. To proceed with this step, first select the shape of the box from the three
basic shapes: cubic, orthorhombic, and triclinic. While selecting, the box size
calculation has two options: (i) buffer—Calculate the size using the given buffer
distance between the solute and the box boundary and (ii) absolute size—Specify
the distance between the solute and the simulation box.
4. Insert the protein into a lipid layer with the setup membrane from system builder
panel if the target system is a membrane protein. DPPC, POPC, and POPE are
the three membrane models supported by Desmond.
5. Calculate the charge of the system. Positive (Na
+ ) or negative (Cl
− ) ions are
added to neutralize the solvated system or to set a desired ionic environment for
the protein.
6. Before MD simulations, relax the whole system into a local energy minimum
either by minimization or by selecting the panel options. In this step, the system is
minimized by the steepest descent method followed by limited-memory BroydenFletcher-Goldfarb-Shanno (LBFGS) algorithms. Generally, two parameters are
set for the minimization: (i) maximum number of iterations and (ii) convergence
threshold for the gradient.
7. Utilize the desmond panel to set the simulation parameters such as production
run, simulated annealing, or replica exchange for the system. The simulation
section is where the user specifies the simulation time (in nanosecond) and the
recording time interval (in picosecond) for the energy calculation and between
the snapshots in the trajectory file. Additionally, selecting the ensemble type
(such as NVT, NPT, NVE, NPγT, and NPAT) to set the temperature, pressure,
and surface tension occurs in the simulation Section.
8. Finally, run the simulation. The resultant trajectory is analyzed by the simulation
quality analysis or the simulation event analysis panel. The result includes a
summary of the simulation and analysis of total and potential energy, temperature,
pressure, and volume throughout the simulation.
10.5 MD Simulation Protocol
An overview of the MD simulation protocol is depicted in Fig. 10.5.