PART - Plumed Automatic Restraining Tool

PART is a command line tool to prevent aggregation between specified residues in a molecular dynamics (MD) simulation. Preventing such aggregation is especially of interest in cosolvent MD simulations with hydrophobic probes. PART will build a PLUMED file based on a strucure file provided by the user. This PLUMED file will contain the necessary lines to prevent the aggregation of the specified residues.

Software Requirements

You will need a molecular dynamics (MD) engine patched with PLUMED. Pick an MD engine of your choice (for example GROMACS) and patch it with PLUMED (for example PLUMED v2.7 install instructions). Make sure that the version of the MD engine is compatible with the PLUMED version. Some MD engines, such as AMBER, do not need to be patched with PLUMED as the default install already includes PLUMED.

You will need a Python distribution with the numpy module. The code was tested using the following versions, but we expect other versions to work as well:

• Python: 3.8.10
• numpy: 1.19.2

Installation

Get the code using:

git clone git@github.com:UAMC-Olivier/PART.git

Now either add PART to your PATH and give PART.py execute permission grants or move the PART.py script to the directory where you wish to use it.

Usage

Basic usage utilizes the following syntax:

PART.py -f <.pdb/.gro of input system> -rp <restraint pairs string> -dp <distance point string> > -o <.dat, output file name> 

The restraints pair string lists all residue type pairs you wish to restrain. Separate the two pair members' residue name by a colon, for example 'P1:P1' to prevent aggregation of P1 molecules. Separate multiple pairs by a comma, for example 'P1:P1,P1:P2,P2:P2' to prevent aggregation between P1 molecules themselves, P1 and P2 molecules, and P2 molecules themselves.

The distance point string should contain all residue names included in the restraints pair list, together with the atom on which to base the intermolecular distance calculation. Separate the residue name and the atomname by a colon. Use for example 'P1:C1' to indicate that P1 intermolecular distances distances should be calculated by calculating the distances between the C1 atoms. It is also possible to use center of masses of molecules, for example 'P1:COM:C1-C2-C3' to use the center of mass of the C1, C2 and C3 carbons. If you have used multiple residue names under -rp, define for each residue a central atom or a COM. Separate each definition by a comma. For example use, P1:C1,P2:C1 to use the C1 atom of P1 and the C1 atom of P2 for the distance calculations.

See the examples under Example Usage for further info and two practical examples.

It is possible to modify the repulsion potential by using the optional input arguments -ul, -k, -exp and -eps. To list the full description of all the keyword arguments use:

PART.py -h

Note that PART program units are different from the units used in the PART paper.

Example Usage

Example systems and output can be found under the Examples folder.

Example 1

To generate the PLUMED file of example 1 (.pdb file of an Amber system, pdb file generated using ambpdb):

PART.py -f complex.solvated.pdb -rp 'P1:P1,P1:P2,P2:P2' -dp 'P1:C1,P2:C1' -o test.dat

This command will create a PLUMED file test.dat with restraints applied between all P1 and all other P1 molecules, between P1 and P2 molecules and between all P2 and all other P2 molecules. The distance calculation will be based on the C1 atoms of P1 and P2. The restraint potential will have default PART parameters.

Example 2

To generate the PLUMED file of example 1 (.gro file of a GROMACS system):

PART.py -f solvated_complex.gro -rp 'BNZ:BNZ,PRP:PRP,BNZ:PRP,MAM:ACE' -dp 'BNZ:COM:C01-C02-C03-C04-C05-C06-H07-H08-H09-H10-H11-H12,PRP:C01,MAM:N01,ACE:C02' -o plumed.dat

This command will create a plumed.dat file that makes sure restraints are applied to prevent aggregation between benzenes (BNZs) themselves, between PRPs themselves, between PRP and BNZ, and between MAM and ACE. The distances are calculated using the COM of all benzene (BNZ) atoms, the C01 atom of PRP, the N01 of MAM and C02 atom of ACE.

Customizing the PLUMED file to add additional restraints

After running PART, you can add additional custom restraints if desired. To add additional restraints to your simulation, open the PART output file (by default plumed.dat) with your favorite text editor. You can now add additional lines in this file to define new restraints. You can consult the PLUMED manual to correctly define your additional restaints.

Citations

If you found PART to be useful in you work, please consider citing the following paper:

O. Beyens, H. De Winter (2024). Preventing lipophilic aggregation in cosolvent molecular dynamics simulations with hydrophobic probes using Plumed Automatic Restraining Tool (PART). Journal of Cheminformatics, 16 (Article number: 23)