DNA-DNA hybridization simulating

User discussions
1

GROMACS version: 2020.6
GROMACS modification: No

Hello guys. I’m a beginner who has recently entered this field and has limited knowledge about GROMACS. I just finished the beginner’s tutorial on lysozyme in water.

I’m interested in simulating DNA-DNA hybridization. In simple terms, I have a 100 nt single-stranded DNA (ssDNA) with a secondary structure (hairpin), as well as several 20-30 nt ssDNAs with sequences complementary to different regions of the 100 nt hairpin DNA. The term “hairpin” refers to the structure of the ssDNA resembling a hairpin, which is significant in some nucleic acid molecular pathways. My major is Nucleic Acid Molecular Circuit Engineering.

hairpin
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I aim to use GROMACS MMPBSA to calculate the key base interactions when these 20-30 nt ssDNAs bind to the 100 nt hairpin DNA with a secondary structure.

I currently have two main questions:

  1. My ssDNA has a hairpin structure, and in a sense, its ideal secondary structure is predetermined (designed based on the subsequent reactions I want to trigger). I’m wondering if I can directly create a pdb file with the secondary structure. However, I’m unsure which software can accomplish this part. Any suggestions would be appreciated.
  2. If option 1 is not feasible, do I need to perform energy minimization first and then proceed with simulating the interaction with other structures? Or are there alternative approaches? Your guidance would be greatly appreciated. (Note: The temperature here is not room temperature.)

I’m certain that I’m looking for a specific DNA-DNA tutorial, but I can’t find relevant literature for my specific question. Most people seem to use GROMACS for simulations related to proteins. Perhaps someone involved in DNA or nucleic acid research can point me in the right direction and suggest resources that would aid my learning?

If you could provide valuable guidance, I would be extremely grateful.

Thank you in advance!!!

2

My experience is by no means complete here, so perhaps I’m missing some promising approaches, but I’d say a combination of folding and hybridization looks like a use case for a general coarse-grained model such as 3SPN.2C (see the FF parametrization paper). There is also a DNA version of Martini but I’m not aware of its widespread use for simulating DNA annealing/hybridization.

While Martini has a Gromacs port and tutorials, 3SPN.2C is available in other packages, most notably OpenMM, Genesis and CafeMol.

I myself had always used X3DNA to create custom nucleic acid models (and continue to do so), but the software was recently incorporated into DSSR and commercialized.

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Thank U!!! I heard X3DNA is uesful but our group… I find that this website http://biophy.hust.edu.cn/new/3dRNA/create ^_^ By the way, I’d like to use the force field AMBER99-ILDN

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hey…were u able to find a solution for this? As i work in a similar research area of nucleic acid networks and was struggling to find a simulation tool