Hello everyone,
Looking for guidance on how to simulate a maybe niche system. It is a protein-oligonucleotide interaction in solution, however the oligo in question is a chimeric strand, meaning some nucleotides are DNA bases and some are RNA bases. I have been able to simulate this system and get reasonable results when the oligo is entirely RNA, however when I change some bases to DNA I get the following error message:
Fatal error:
The residues in the chain DT1āRC78 do not have a consistent type. The first
residue has type āDNAā, while residue RG21 is of type āRNAā. Either there is a
mistake in your chain, or it includes nonstandard residue names that have not
yet been added to the residuetypes.dat file in the GROMACS library directory.
If there are other molecules such as ligands, they should not have the same
chain ID as the adjacent protein chain since itās a separate molecule.
Which makes sense in retrospect since its changing residue type halfway through. However, since we technically have the parameters for each possible nucleotide, I wanted to check if it is possible to āmergeā the DNA and RNA force fields into one and if people are aware of a method/tool to do so. Alternatively, Iām open to any suggestions from people on how to handle such a system. For reference, Iām using the AMBER ff14sb and XOL3 and OL15 forcefields.
Still interested in this if people have answers. I have tried manually merging force fields but the charges become non-integer. Therefore, if people know how to correct the charges of custom force fields that would also be helpful.
So Iāve tried briefly to see if I could get it to work, turns out this isnāt an issue with the forcefields, itās something that comes with gromacs. The file āresiduetypes.datā is included in the gromacs installation and basically lists which residues can be linked into a single molecule. Youād need to find and modify this file to get this to work.
Iāve tried creating a conda environment where I install gromacs and edit the residuetypes.dat, and pdb2gmx seems to work if all the RNA residues in residuetypes.dat are listed as DNA instead of RNA, but Iām not enough of an expert in the program to know whether or not this will cause issues later on during the simulations.
(Also, since this requires editing the files in the gromacs folder rather than just altering the forcefields, this would have to be done on some separate installation that wouldnāt affect any of your other projects)
Hi thanks for your answer. Yes, I was able to copy the force field and residuetypes.dat file to my working folder so it uses both of these custom versions when selecting the field as I create the topology. I edited the residuetypes.dat so that it reads everything as RNA. The charges are still slightly off by 0.0002 from an integer. If you manually rebalance on the topol_RNA_chain.itp file by that small charge then my simulation ran fine and the results made sense based on what I expect from my experimental data and what I know from this system.
@scinikhil The problem is that this doesnāt seem to be an issue with a mismatch between coordinate file and forcefield, gromacs uses residuetypes.dat independent of which forcefield is chosen, and it doesnāt allow for a chimeric strand where DNA and RNA exists within the same molecule unless residuetypes.dat is modified