You need two different structures/conformers of a protein, A and B. These structures need to be equilibrated in Molecular Dynamics (MD), preferably in the presence of explicit solvent (and also membrane if a membrane protein is simulated).
In this tutorial we will use Adenylate Kinase (AK) as an example. Files in the following archives can be used to follow this tutorial:
The scripts in those folders can be used to perform coMD for any other system.
I strongly suggest that you take a quick look into these folders. What subfolders do you have? What type of files are in those folders? Obtain an overview of the files.
Prior to generating the first sets of ANM modes perform as many minimization steps as you do in the MD scheme of the coMD cycles to be consistent with them.
As mentioned before you need to equilibrate your states A and B. Subsequently, perform a short minimization, which is 500 steps for the tutorial example, and put the restart files into the folders 500i and 500f.
Please open the file main2/main2.m inside the coMD folder.
In order to attain a specific MC/Metropolis acceptance ratio the parameter a inside the MC/Metropolis condition (see below) has to be set accordingly:
If the MC/Metropolis acceptance ratio exceeds or falls below our desired ratio then a is adjusted inside the code as follows:
if prevper(2)>0.95 a=prevper(5)*1.5; elseif prevper(2)<0.85 a=prevper(5)/1.5; end
Here 0.85 and 0.95 refer to the lower and upper limits of a %90 MC/Metropolis Acceptance ratio simulations. These numbers can be adjusted according to the users preference.
In its current form a is adjusted if the acceptance ratio becomes larger than %95 or lower than %85.
In order to initialize a coMD simulations are performed without their Targeted MD + Minimization part.
The script used to initialize the parameters for AK can be found here.
Go into this folder and simply submit the shell script main.sh by typing the following command into the terminal:
nohup sh ./main.sh > main.out &
Once the initialization simulations has converged take the oran.dat and oranr.dat files inside the folders main2 and main2r, respectively, and put them into your main coMD simulation folder (under main2 and main2r).
There are four types of pgn files that coMD uses:
align_start_with_final_structure.pgn CA_final_structure.pgn tmd_target_structure.pgn RMSDchecker.pgn
align_start_with_final_structure.pgn aligns the current conformer with its target.
CA_final_structure.pgn generates the target pdb’s for MC/Metropolis Simulations with Carbon Alpha (CA) coordinates only.
tmd_target_structure.pgn generates the target pdb’s for Targeted Molecular Dynamics Simulations.
PLEASE NOTE THAT YOU NEED PDB FILES (CA.pdb and CAr.pdb) THAT CONTAIN AS MANY CA ATOMS AS YOUR MC/METROPOLIS ALGORITHM USES.
Above the pgn files for the A–>B direction were discussed. The same files exist for the B–>A direction, which have simply an additional “r” endings .
Please note the number of CA atoms to be displaced has to be the same for states A and B.
If they are not, then you need to change the pgn scripts (see below) so that the selections have the same number of CA atoms.
This is really much easier than it sounds. You simply define instead of:
[atomselect "name CA"]
[atomselect "resid xxx to yyy and name CA"]
Open a terminal and go into the coMD folder . Simply submit the shell script main.sh by typing the follwing into the terminal:
nohup sh ./main.sh > main.out &
Please note that intermediate conformers in those dcd files are ordered such that the first frame of the B–>A trajectory follows the last frame of the A–>B trajectory.
In addition you have to adjust these pgn files with respect to the total number of coMD cycles. This is described inside the pgn files.