MDtutorial_DSx

throneharshΒιοτεχνολογία

2 Οκτ 2013 (πριν από 4 χρόνια και 12 μέρες)

63 εμφανίσεις

1


Molecular Dynamics (MD)
Simulation of Protein
-
Ligand Complex using
Discovery Studio 2.0

Input
files:

Protein

= EGFRTK.pdb



Ligand

= aq4.mol2


1.

Open D
iscovery
S
tudio 2.0

2.

Open input files

2.1.

Go to “Files” explorer

2.2.

C
lick
EGFRTK.pdb

and aq4.mol2















3.

Create protein
-
ligand complex file

3.1.

Go to “aq4


3D Window”

3.2.

Copy all atoms of aq4.mol2

3.3.

Paste onto EGFRTK


3D Window














3.4.

Drag AQ4 atoms into EGFRTK atoms










2


3.5.

Save the new complex as “EGFRTK
-
AQ4.msv” and close

aq4


3D Window


















4.

Assign forcefield parameters to all atoms

4.1.

Go to “Tools” explorer

4.2.

Select “Simulation” and click the dropdown arrow for “Forcefield”

4.3.

Select “CHARMm” and click “Apply Forcefield”













5.

Solvate the complex with explicit water

5.1.

Go to
“Protocol” explorer

5.2.

Double click on “Simulation” and then “Solvation”
















3


5.3.

Set the parameter

Input Typed Molecule

EGFRTK
-
AQ4
: EGFRTK

Solvation Model


Explicit Spherical Boundary with Harmonic Restraint


Radius of Sphere


20.0


Center of Mass


EGFRTK
-
AQ4
: EGFRTK












5.4.

Click the run button











5.5.

Read the solvated complex in Output Files named “EGFRTK.msv”
















6.

Set up the standard molecular dynamics simulation

6.1.

Go back to “Simulation” on “Protocol” explorer

6.2.

Double click
“Standard Dynamics Cascade”




4
















6.3.

Set the parameter




















6.4.

Click the run button

















5


Analysis of MD Simulation


1.

P
lay

the molecule
s

1.1.

Read all conformation

in Output Files named “EGFRTK.msv”

1.2.

Click play

to start animation















2.

Analyze overall trajectory

2.1.

Total energy

-

Go to “Simulations” on “Tools” explorer

-

Double click “Analyze Trajectory” and then click “Create Plot”

-

Choose X axis as “Time”
and Choose Y axis as “Total Energy”














-

See
the result













6


2.2.

RMSD of protein backbone

-

Go to “Simulation” on “Protocol” explorer

-

Double click “Analyze Trajectory”

-

Set the parameter
















-

Click the run button

-

Read output file
“EGFRTK.msv”


-

Go to “Simulations” on “Tools” explorer

-

Double click “Analyze Trajectory” and then click “Create Plot”

-

Choose X axis as “Time” and Choose Y axis as “backbone RMSD”












-

See the result















7




3.

Calculate interaction energy
between protein and ligand

3.1.

Create the group for ligand

-

Click to select the ligand “AQ4”

-

Go to “Edit” on menu bar and select “Group”

















-

Name this group as “Ligand”









3.2.

Create the group for amino acid residue (e.g. Met769)

-

Click to
select the amino acid “MET769”

-

Go to “Edit” on menu bar and select “Group”

-

Name this group as “M769”

















8


3.3.

Calculate interaction energy between “Ligand” and “Met769”

-

Go to “Simulation” on “Protocol” explorer

-

Double click “Calculate Interaction

Energy”













-

Set the parameter











-

Click the run button


3.4.

Read

the final interaction energies (kcal/mol)


















Van der Waals Energy

Electrostatic Energy

Total Energy

Met769

-
2.31977

3.95088

1.63110



9


3.5.

Get the interaction
energies along trajectory

-

Go to “Simulations” on “Tools” explorer

-

Double click “Analyze Trajectory” and then click “Create Plot”

-

Choose X axis as “Time” and Choose Y axis as “backbone RMSD”
















-

See the result