Bash script to automate setup of multiple identical MD simulations. MD parameters are for the amber-type forcefields such as amber99sb-ildn and amber03ws.

GROMACS is used. Any recent version should work. To install GROMACS, download it, extract it, and build from source with GPU support. Check gmx --version to see if everything works (GPU/cuda properly recognized? etc.).

In linux:

git clone https://github.com/yurayura-nmr/chikaterasu.git

1. Put PDB file of your system to be simulated into ./gromacs/coord/ [e.g. 1UBQ.pdb]
2. Edit the top section of chikaterasu.sh to specify its filename [e.g. 1UBQ]
3. Set MD parameters for NVT, NPT, and production MD in chika_mdp/~.mdp files [time, temperature, amounts of frames saved, etc.]
4. For a new system, run chikaterasu at various levels to confirm no errors in preparation/execution of MD simulation. If the system is already known to behave well, can go straight to a full run (level 0) and skip the individual levels (1-6).

Run chikaterasu at level 1:

sh chikaterasu.sh 1
# Tests if pdb format to gromacs conversion works. Make sure no errors or warnings are given by GROMACS.

Run chikaterasu at level 2:

sh chikaterasu.sh 2
# Tests if protein could be solvated in the box. Make sure no errors before continuing.

Run chikaterasu at level 3:

sh chikaterasu.sh 3
# Tests if ...

Run chikaterasu at level 4:

sh chikaterasu.sh 4
# Tests if ...

Run chikaterasu at level 5:

sh chikaterasu.sh 5
# Tests if the first equilibration step (100 ps of NVT position-restrained simulation) is working without any issues. From here on the GPU is actually used. Sometimes the nvidia driver disconnects itself and will require a reboot before working again.

Run chikaterasu at level 6:

sh chikaterasu.sh 6
# Tests if all equilibration steps including the final 100-ps NPT position-restrained simulation are working without any issues.

Finally, run chikaterasu at production level (0):

sh chikaterasu.sh 0
# Starts production MD

Coordination bonds are formed between Lewis acids (e.g., Zn2+) and Lewis bases (e.g., thiol groups R-S-H or R-S(-)). Lone pair electrons on S atom to Zn2+ d-orbital.

The example here is written for the case of Zn2+ ions bound to a protein in the input PDB file. Similar steps should work for other ions (Ca2+, Mg2+, etc.).

Choose 2 coordinating Cys residues and define them as CYM (instead of CYS) in the PDB file to ensure local charge neutrality (Zn2+ + Cym- + Cym-). For this example, let us assume that CYS residues Cys197 and Cys214 were chosen as CYM residues. Cys200 and Cys211 are chosen as regular CYS residues.

Now we need to topology:

./chikaterasu.sh 1   # this should run normally

Now the topology is already accessible in gromacs/top. We can see the atom numbers as defined by GROMACS (not the PDB file). Find the atom number of the Zn2+ ion and note it down (let's say, it is 3358). This will be used soon. Also find the atom numbers of all the coordinating (e.g., S-gamma atoms of Cys residues. Let us say for this example, they are 2564, 2595, 2768, and 2811.

In the chikaterasu base folder, provide an additional file containing the distance restraints for the Zn2+ ion (e.g., to coordinating His or Cys residues). As an example distance_restraints.itp file:

#ifdef DISRES
[ distance_restraints ]
; ai aj type index type’ low up1 up2 fac
  2564 3358   1   1     1     0.0 0.23 0.3 1      ; CYM197 SG <> Zn2+
  2595 3358   1   2     1     0.0 0.23 0.3 1      ; CYS200 SG <> Zn2+
  2768 3358   1   3     1     0.0 0.23 0.3 1      ; CYS211 SG <> Zn2+
  2811 3358   1   4     1     0.0 0.23 0.3 1      ; CYM214 SG <> Zn2+
#endif

Next, in chikaterasu.sh, set the distance restraints flag to true:

distance_restratints=true

Finally, we need some Zn2+-protein bonds. Make another file called "metal_protein_bonds.top" or something like that:

2564  3358     6 0.24  4000    ; 16 CYS-SG G-C-T
2595  3358     6 0.24  4000    ; 13 CYS-SG Q-C-P
2768  3358     6 0.24  4000    ; 27 CYS-SG G-C-E
2811  3358     6 0.24  4000    ; 30 CYS-SG G-C-C

Now, unfortunately, this file (containing the coordination bonds between the Zn2+ atom and Cys S-gamma atoms) is not yet automatically integrated into final topology file topol.top.

At present, Chikaterasu will pause once to give the user the chance to ninja-edit the topol.top by adding these special bonds, right before going to energy minimization. (i.e., just copy paste these 4 lines into topol.top).

In the future, this will be automated so that the metal_protein_bonds.top file is read automatically into topol.top and this user-invention is not required.

1. Go to: https://modbase.compbio.ucsf.edu/modloop/
2. Using registered email address and license key - MODELIRANJE
3. Upload coordinate file - file.pdb

Enter loop segments (residue:chain_ID:residue:chain_ID):

70:A:71:A:

For that the uploaded pdb file needs to be tuned so that (in this example) ALA71 already exists. i.e., add dummy atoms like this in a text editor (positions should not matter and probably can even be 0 0 0):

ATOM    556  N   ALA A  71      32.763  35.831  23.090  1.00 12.71           N
ATOM    557  CA  ALA A  71      34.145  35.472  23.481  1.00 16.06           C
ATOM    558  C   ALA A  71      34.239  35.353  24.979  1.00 18.09           C
ATOM    559  O   ALA A  71      33.707  36.197  25.728  1.00 19.26           O

Added just another folder for user-specific (non-automatable specific) analysis. (not overwritten by the cleanup function)

Such as specific PCA of only atoms 1-70 of Ub2. Or just 1 basepair of a DNA.

Added Mg ion functionality [tested a bit, but may still have bugs]

Added insert molecules [tested a bit, but may still have bugs]

• Issue warning if low on disk space before starting a new run.
• ss untested and only implemented for His=false yet
• re-add dssp function:
• gmx xpm2ps -f ss.xpm -di dssp.m2p