MOLECULAR DYNAMICS

Denise Chac 25 November 2014

PI: Dr. Ha Youn Lee

WHAT IS MOLECULAR DYNAMICS?

A computer simulation of physical movements of atoms and molecules in the context of N-body simulation - Wikipedia

Method of screening theories before applying them to the real world … a computer experiment - Frenkel and Smit

WHY MOLECULAR DYNAMICS?

Pros:

Predict properties of materials

Predict new properties

Data Analysis

Exploratory Tool

Cons:

Computationally demanding

Hard to model large systems

Additional research/experiments necessary

AMBER

Assisted Model Building with Energy Refinement

Sander — Simulated annealing with NMR-derived energy restraints

CASE STUDY: GP120

HIV - Human Immunodeficiency Virus

envelope glycoprotein

Function - attachment to host cell’s cell surface

OUTLINE:

1. Molecule

2. Start Files

3. Input Files

4. Running the Simulation

5. Visualization

6. Analysis

1 - MOLECULE

tleap

$ source leaprc.ff03

$ gp120 = loadpdb 1MEQ.pdb

$ solvatebox gp120 TIP3PBOX 10.0

2 - START FILES

$ saveamberparm gp120 prmtop inpcrd

prmtop = the file containing the parameters and topology

inpcrd = the file containing the coordinates

3 - INPUT FILES

$ gedit min.in

$ gedit heat.in

$ gedit prod.in

3 - INPUT FILES

$ gedit min.in

To minimize the system of the molecule gp120 within the solvate box

3 - INPUT FILES

$ gedit heat.in

NVT system

constant number of particles, volume, and temperature

Run simulation for 20 ps from 0K to 300K

Temperature managed using Langevin thermostat

3 - INPUT FILES

$ gedit prod.in

NPT system

Constant number of particles, pressure, and temperature

Temperature: 300K

Pressure: 1 atm

Run simulation for 60 ps

4 - MD SIMULATION

$ sander -O -i input.file -o output.file -p prmtop -c inpcrd -r restart

-i = name of input file

-o = name of output file

-p = parameter/topology file

-c = set of initial coordinates for MD simulation

-r = final set of coordinates for MD simulation

5A - VISUALIZATION

VMD = Visual Molecular Dynamics

File > New Molecule

Browse > prmtop

as AMBER7 parm

Browse > Prod.mdcrd

as Amber Coordinates with Period Box

5B - VISUALIZATION

VMD = Visual Molecular Dynamics

Extensions > Visualization > Movie Maker

Renderer: Snap Shot

Movie Settings: Trajectory

Format: JPEG Format

5C - VISUALIZATION

6A - ANALYSIS

$ process_mdout.perl Heat.out Prod.out

gnuplot>

$ plot Summary.TEMP

$ plot Summary.ETOT/EKTOT/EPTOT

6B - ANALYSIS

$ ptraj prmtop rmsd.ptraj > ptraj.log

rmsd.ptraj

Calculate RMSD between the initial structure and final structure

REFERENCES

Frenkel, D. & B. Smit. 2002. Understanding Molecular Simulations: from algorithms to applications. 2nd Edition. Academic Press: London, UK.

Case, D.A. et al. 2014. Amber 14 Reference Manual. Park, M., Park, S.Y., Miller, K.R., Collins, E.J., Lee, H.Y., 2013. Accurate Structure

prediction of peptide-MHC complexes for identifying highly immunogenic antigens. Molecular Immunology 56, 81-90.

Alberts, B., Johnson, A., Lewis, J. et al. 2002. Molecular Biology of the Cell. 4th Edition. New York: Garland Science.

Janeway, C., Murphy, K., Travers, P., Walport, M. 2008. Janeway’s Immunobiology. 8th Edition. New York: Garland Science .

Guilhaudis et al. 2002. Solution structure of the HIV gp120 C5 domain. Euro J Biochem 269: 4860-4867.