MD Simulation for Small Molecule aggregation

User discussions
1

GROMACS version: 2024.4
GROMACS modification: No

I would like to check the driving forces for the nanoaggregation of small organic molecules in the aqueous solution. Experimental results indicated the nanoaggregate formation. I am completely new to the GROMACS and could not find a tutorial for this purpose. How shall I perform the simulation to check the aggregation process.

2

This should be rather straightforward. Create an initial coordinate file with molecules dispersed in the box and then add water using gmx solvate. Plain MD simulations will show whether and how the molecules aggregate. But not that you do need a force field that accurately describes the interactions between the molecules and between the molecules and water.

3

Thanks for the input. I am relatively new to the gromacs and learn several new things daily. If you could share any simple protocol, I would be grateful. Basically, I could generate the .itp and .pdb files from swissparam using .mol2 files. Further, I know how to generate the box and add water, ions to the box, including a ligand. However, I have not yet generated the correct topology file. I am stuck at this step. I wish to use Charm forcefield for initial experiments, which will eventually be changed to amber once I learn to make a first small md run.

4

I could generate a correct topology file that allowed a successful NVT and Npt optimizations of 1 ns each. However, what i wonder is, how to keep all freely moving molecules including ligands and solvents in the box while limiting their free movement inside the box. Ideally for protein ligand interaction Protein_Ligand and Water_SOL_IONS are made a group in nvt, npt, and md optimizations. How should i set this interaction parameter where i want to the interaction between the multiple ligand (same) molecules.

5

I don’t understand your question. All molecules in the system interact with all other molecules. There is nothing special to do when you want to observe aggregation. You might be able to speed up the aggregation by keeping e.g. a ligand close to a protein using a restraint, but that can be tricky.