Comprehensive, hands-on tutorial for DNA-ligand MDS

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GROMACS version: 2021.4-Homebrew
GROMACS modification: No

Hello, guys. I am very new to molecular dynamics and I come from biomedical background. Recently, my boss asked me to gather additional data about interaction of a small molecule and an aberrant double-stranded DNA structure. I originally did docking experiments in Vina, and he wants to complement the data with results from GROMACS. I have structure files of both DNA and ligand in PDB format, so that is my input. I managed to created topology files, a simulation box and fill it with water. However, I don’t know what to do next and I’m pretty sure I did something wrong at some point because it throws me errors no matter what I do downstream of that.

I’m pretty sure the problem is that I’m following tutorials that are tailored for protein-ligand MDS, hence my question: is there any good, detailed tutorial for DNA/nucleic acids-small molecules MDS? It is extremely hard to find for some reason. The vast majority of people seem to use GROMACS for protein-related simulations. Maybe there is someone who works with DNA or nucleic acids in general who can point me in the right direction, towards resources that would help me learn? Or at least give some overall tips of parameters and commands specific to nucleic acid MDS? For example, by reading some literature, I found out that I need to specify a specific type of CHARMM forcefield if I’m working with DNA… even general tips like that would be very helpful.

Thank you in advance.

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I don’t know of such a tutorial, but in a practical sense, there’s really no difference from simulating a protein:ligand complex. Things like .mdp settings are not sensitive to the chemical nature of the solute. Once you’ve generated the topology (DNA can natively be generated by pdb2gmx), the steps are largely the same.

If you’re getting specific errors, please post them and ask questions.

I would say that (even as a CHARMM guy :) the AMBER force fields are the standard for nucleic acid simulations, though GROMACS does not include any of the recent versions by default, and the ones it has are wildly outdated. CHARMM is a good force field, but AMBER tends to be somewhat better in this context.

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Hello! May I ask how you get the pdb format of your DNA？ I mean is your DNA designed by yourself？I designed some ssDNA which have second structure but I don’t know how to get pdb format with second structure. Or can you give me any suggestion about DNA? Hope your reply!!

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ChimeraX has a feature that allows to build DNA sequences and save as pdb.

Launch ChimeraX then select: Tools>Structure Editing>Build Structure

A new window called “Build Structure” will open, listed on the left of this window are all the different options, select “Nucleic Double Helix” and enter your sequence. A little fiddling with the model and you can make all sorts of different structures.