Molecular Dynamics Simulations Analysis of Glucocerebrosidase

Introduction

To analyze our Molecular Dynamics Simulations we followed the tutorial described here: http://md.chem.rug.nl/~mdcourse/analysis1.html

Wildtype

A brief check of results

• command: gmxcheck -f 2NT0_wt_md.xtc

How many frames are in the trajectory file and what is the time resolution?

• 2001 frames
• timestep: 5ps

How long did the simulation run in real time (hours), what was the simulation speed (ns/day) and how many years would the simulation take to reach a second?

• Simulation run: 8h37:36
• Simulation speed: 27.821
• Time to reach a second: 1/0.000000028 = 35714285,714285714 days = 97847,358121331 years

Which contribution to the potential energy accounts for most of the calculations?

• -9.39801e+05 kJ/mol

Visualization of results

For visualization we extract 1000 frames from the trajectory (-dt 10), only select the protein without the water and remove the jumps over the boundaries to make a continuous trajectory (-pbc nojump).

• command: trjconv -s 2NT0_wt_md.tpr -f 2NT0_wt_md.xtc -o protein.pdb -pbc nojump -dt 10

Figure 1: The protein with the spectrum

Figure 2: The protein with the box around it

Figure 3: The cartoon presentation after using the command dss

Figure 4: The active site

STILL MISSING: movie

Quality assurance

Convergence of energy terms

First we look at the energy terms. Therefore we look at the temperature, the pressure, the energy, the volume, the density, the box and the interaction energies between protein and solvent (Coulomb and van der Waals).

With the following commands we produced *.xvg files which were visualized with xmgrace.

g_energy -f 2NT0_wt_md.edr -o temperature.xvg
g_energy -f 2NT0_wt_md.edr -o pressure.xvg
g_energy -f 2NT0_wt_md.edr -o energy.xvg
g_energy -f 2NT0_wt_md.edr -o volume.xvg
g_energy -f 2NT0_wt_md.edr -o density.xvg
g_energy -f 2NT0_wt_md.edr -o box.xvg

Temperature

Figure 6: Temperature of the Molecular Dynamics Simulation of the Wildtype

Energy Average Err.Est. RMSD Tot-Drift
Temperature 297.912 0.0062 1.08924 0.00616934 (K)

What is the average temperature and what is the heat capacity of the system?
297.912

Pressure

Figure 7: Pressure of the Molecular Dynamics Simulation of the Wildtype

Energy Average Err.Est. RMSD Tot-Drift
Pressure 1.00032 0.014 87.9016 0.0583997 (bar)

Estimate the plateau values for the pressure.
1.00032

Energy

Figure 8: Energies of the Molecular Dynamics Simulation of the Wildtype

Energy Average Err.Est. RMSD Tot-Drift
Potential -939801 85 924.013 -583.172 (kJ/mol)
Kinetic En. 170900 3.6 624.851 3.53909 (kJ/mol)
Total Energy -768901 84 1128.21 -579.63 (kJ/mol)

What are the terms plotted in the file energy.xvg?
potential, kinetic and total energy

Volume

Figure 9: Volume of the Molecular Dynamics Simulation of the Wildtype

Energy Average Err.Est. RMSD Tot-Drift
Volume 735.655 0.042 0.552925 -0.0802412 (nm^3)

Estimate the plateau values for the volume.
735.655

Density

Figure 10: Density of the Molecular Dynamics Simulation of the Wildtype

Energy Average Err.Est. RMSD Tot-Drift
Density 1009.64 0.058 0.75885 0.110104 (kg/m^3)

Estimate the plateau values for the density.
1009.64

Box

Figure 11: Boxes of the Molecular Dynamics Simulation of the Wildtype

Energy Average Err.Est. RMSD Tot-Drift
Box-X 10.1328 0.0002 0.00253864 -0.000368389 (nm)
Box-Y 10.1328 0.0002 0.00253864 -0.000368389 (nm)
Box-Z 7.16498 0.00014 0.00179508 -0.000260487 (nm)

What are the terms plotted in the file box.xvg?
the sizes of the box around the protein

Interaction Energy: Coulomb

Figure 12: Interaction energy of protein and solvent

Energy Average Err.Est. RMSD Tot-Drift
Coul-SR:Protein-non-Protein -24690.5 120 476.146 -405.451 (kJ/mol)
Coul-14:Protein-non-Protein 0 0 0 0 (kJ/mol)

Interaction Energy: van der Waals

Figure 13: Interaction energy of protein and solvent

Energy Average Err.Est. RMSD Tot-Drift
Coul-SR:Protein-Protein -23823.8 63 232.842 -193.75 (kJ/mol)
Coul-14:Protein-Protein 95543.6 68 227.139 424.841 (kJ/mol)

Mutation 7

still waiting

Mutation 10

still waiting