Rebuilding Z-DNA

[shr]

I was wondering if there is a way to rebuild Z-DNA with rebuild module in the local installation of x3DNA. I know it works for B-DNA and A-DNA and I can make a Z-DNA fiber model as well but I couldn't find a direct way to extend an existing Z-DNA structure. Is there a workaround which I can try? Thank you in advance.

[xiangjun]

Hi,

Thanks for using 3DNA and for posting your questions on the Forum. 3DNA rebuild should be able to build Z-DNA structures given a set of parameters. Please be specific with what you are trying to achieve, and we can start from there.

Best regards,

Xiang-Jun

[shr]

I have a PDB structure of Z-DNA-protein complex that I wanted to simulate. Before simulation, I wanted to make the DNA longer to avoid the issue of the protein interacting with any of the terminal bases. I can use the following commands to achieve this in case of B-DNA:

find_pair 1MNN.pdb 1mnn.bps
x3dna_utils cp_std bdna
rebuild -atomic bp_step.par extended_dna.pdb

But x3dna_utils does not take zdna as an argument so I was wondering how I can do it?

[xiangjun]

Thanks for your quick follow-up.

As noted in the x3dna_utils cp_std -h help message, the utility covers the most common use cases:

Select the standard data files to be used with "analyze" and "rebuild".
Available sets include BDNA, ADNA, NDB96 and RNA, which have exactly
the same base geometry and orientation (in the standard base reference
frame) but different backbone conformations.

Z-DNA is different from the standard right-handed DNA/RNA double helix in that it has not only a left-handed twist but also a base flip, and it has a di-nucleotide (most commonly CpG) as a the building block. So the x3dna_utils cp_std does not cover Z-DNA. However, you can run analyze, modify the output parameters (and extend as needed), and then rebuild a Z-DNA structure according to the modified parameters.

What specific Z-DNA structure you’d like to extend? If you do not want share details, please use a sample Z-DNA structure that helps illustrate your point. Reproducibility is important.

Best regards,

Xiang-Jun

[shr]

Thank you for your quick responses!
My input structure is the PDB structure 1QBJ. It is a 6nt DNA. I have attached a picture. Without using the x3dna_utils, even without extending, the backbone cannot  be modelled due to the distance of O3' and P being over 4.5 and throws the following error. However, I also tested with the fiber model of Z-DNA to understand how it works with Z-DNA. I found that besides the backbone not being modelled which is because of the PDB dataset not being since I'm not using x3dna_utils, rebuild could model the bases as separate molecules. So, this is possibly the issue with my Z-DNA crystal structure model.

Another observation was, previously, for the crystal structure of BDNA complexed with the protein, I tried to manually extend the DNA in pymol but due to the terminal base positions, I could not properly build the double helix. But after analyze and rebuild, I could. So I assume it is due to standardization of the structure after rebuild. However, there is a problem with this method for Z-DNA. Even if I manage to standardize the structure, pymol does not offer building Z-DNA. So, I was wondering if I could add the extended DNA before rebuild. As you suggested, I modified the bp_step.par file since that is the file used as input for rebuild. Is that the correct way? I apologize if I am asking too many questions.   

[xiangjun]

Thanks for your follow-up questions and the details you provided. It is always helpful to to be specific when discussing research topics.

Yes, "rebuild -atomic" would have issues with backbone connectivity, since in Z-DNA, nucleotide G is in syn conformation instead of anti (for C). The building block must be adjusted accordingly. I'll look into this further to see what we can get.

Another approach is to take the whole Z-DNA structure as a unit, and perform some transformations to extend it. See the PyMOL thread a few years ago on "create a 26 bp RNA from a 13 bp system" (https://www.mail-archive.com/pymol-users@lists.sourceforge.net/msg16190.html). The idea is applicable to Z-DNA as well. Note that the features are now available in the free DSSR Academic license (previously in DSSR Pro Academic only). Check if that method makes sense to you.

Best regards,

Xiang-Jun