Recent Posts

81

RNA structures (DSSR) / Re: Rebuilding circular Z-DNA

« Last post by xiangjun on April 25, 2025, 07:40:54 am »

Hi Di,

This looks good. Please provide the commands used to generate the structures, for example, as I did in the blogpost on "Building extended Z-DNA structures with backbones using DSSR". Every detail counts for reproducibility.

Moreover, I would also consider the case where C-G pairs instead of G-C pairs are present in the structure. Or all 168 pairs with CGCG... sequence. I've thought about the case, and I think what we are trying to acheive fit under the general category of mutated backbones, given the atomic coordinates of base atoms. This is in contrast to the mutating bases feature currently implemented in `mutate_bases` in 3DNA and the `x3dna-dssr mutate` subcommand in DSSR.

Best regards,

Xiang-Jun

82

RNA structures (DSSR) / Re: Rebuilding circular Z-DNA

« Last post by Di_Liu on April 25, 2025, 02:12:11 am »

Hi Xiang-Jun,

I manually aligned 5 dimer units onto the circle. As expected, it works. Only very minor adjustment of bond angles and lengths are required later. I'm attaching the screenshot and the pdb file.

Di

83

RNA structures (DSSR) / Re: Rebuilding circular Z-DNA

« Last post by xiangjun on April 24, 2025, 11:07:20 pm »

Hi @Di_Liu,

I tried to make some progress on constructing a 168-bp circular Z-DNA structure. What I have achieved so far is determining the positions of the repeating units (each being a CG dimer) along the ring. Each position currently serves as a placeholder (a G:C pair; 84 in total), to be replaced by a Z-DNA dimer unit.

I'm attaching a screenshot of the current structure, as well as the corresponding PDB file. I think Xiang-Jun might be able to work his "tasks" magic to align and insert the Z-DNA dimer units into the specified positions.

Nice progress! Using DSSR, I can see clearly the 84 isolated G-C pairs along the circular structure. I will consider adding an option to "x3dna-dssr tasks" subcommand to replace these G-C pairs with GpC dinucleotide steps. Before doing that, it helps to manually replace a few of these G-C pairs with GpC steps to see how the structure looks like. These examples would also server as test cases to validate the new option.

If you think this direction makes sense, I’d be happy to post the detailed process of how I constructed this circle.

Yes, it does make sense. Please go ahead and post the details of your construction process. It may take several iterations to get the desired results. The more concrete our discussions are, the better we can understand each other.

Best regards,

Xiang-Jun

84

RNA structures (DSSR) / Re: Rebuilding circular Z-DNA

« Last post by xiangjun on April 24, 2025, 10:50:29 pm »

Hi @shr,

My work focuses on molecular dynamics simulations of Z-DNA and its interactions with binding proteins. I'm particularly interested in understanding the mechanisms that stabilize Z-DNA, which is inherently less stable than B-DNA. To explore this, I used the crystal structure of the ADAR1 protein bound to a short Z-DNA segment. Since the original segment was quite short, I wanted to extend the Z-DNA backbone. With your help, I was able to successfully simulate this extended structure.

Thanks for the background information about your work on Z-DNA structure. I am glad to hear that the extended Z-DNA structure allowed you to perform your simulations.

However, I encountered challenges in reproducing the specific protein–Z-DNA interactions observed in the crystal structure during my simulations. I believe this is due to multiple non-specific interactions forming between the DNA and the protein, which may mask or override the specific contacts I'm trying to study. It is not a Z-DNA remodeling problem but I am working on understanding Z-DNA stability.

Thank you for sharing your story. Z-DNA modeling is just the first step in understanding its role in biological processes. The other part is beyond the scope of DSSR.

In addition to Z-DNA, I also work on other non-canonical DNA structures, particularly G-quadruplexes (G4s). I’m developing a method to construct ideal G-quadruplex models from sequence data by first arranging guanine bases into tetrads, then building in the backbone and loop regions.

I am glad to hear about your work on G-quadruplexes. Actually, I have recently revised the G4 module in DSSR, fixed existing bugs, and added new features. The g4.x3dna.org website has undergone a complete overhaul, enabling users to upload their own structures for dynamic G4 analysis. Additionally, the DSSR-G4DB database is being actively updated on a weekly basis as new PDB entries are added. See the four blog posts comparing DSSR with other related analysis tools on G-quadruplexes: ASC-G4, Webba da Silva nomenclature, ElTetrado and related tools, and CIIS-GQ.

Moveover, I am also interested in modeling G-quadruplexes, taking G-tetrad as the building block. There are quite a few other threads in DSSR I'd like to pursue further in the future. I'd certainly like to hear more about your approach on modeling G-quadruplex.

As @Di_Liu suggested, I believe a similar model-building strategy could be applied to Z-DNA, to help generate consistent and realistic structures. What do you think about this approach or direction?

Yes, I believe the underlying principles can be generally applicable, including Z-DNA or right-handed A-/B-DNA. The approach in "Building extended Z-DNA structures with backbones using DSSR" is virtually the same as the one used for "create a 26 bp RNA from a 13 bp system".

Please provide more details. Working together with @Di_Liu, we should be able to come up with some interesting results.

Best regards,

Xiang-Jun


Best regards,

Xiang-Jun

85

General discussions (Q&As) / Re: Rebuilding Z-DNA

« Last post by xiangjun on April 24, 2025, 08:30:01 am »

I apologize once again.

I appreciate your attitude and the effort you put into bringing up this interesting topic on the Forum. This case also reminds me that I should be a bit more proactive in engaging with users like you. I always respond directly to users' questions, no matter how minor. Whenever necessary, I ask for clarification to ensure I understand and address their issues correctly. However, if there’s no response, I normally shy away from pushing users further—even though I may have done extra work to make sure I’m on the right track.

I look forward to the blogpost and will check out the thread "Rebuilding circular Z-DNA".

Done. Please see the blogpost Building extended Z-DNA structures with backbones using DSSR. Following the steps in the blogpost, users should be able to build extended Z-DNA structures exactly as described.

I would be happy to contribute in any way I can.

I noticed your follow-up post and the one from @Di_Liu on the new thread Rebuilding circular Z-DNA under the section 'RNA structures (DSSR).' This kind of participation is exactly what I have in mind for the forum. I will get back to you over there soon.

Working together, we should be able to come up with a solution that not only solves the problem at hand but also benefits the community. DSSR would become even more powerful!

Best regards,

Xiang-Jun

86

RNA structures (DSSR) / Re: Rebuilding circular Z-DNA

« Last post by Di_Liu on April 23, 2025, 06:49:40 pm »

I tried to make some progress on constructing a 168-bp circular Z-DNA structure. What I have achieved so far is determining the positions of the repeating units (each being a CG dimer) along the ring. Each position currently serves as a placeholder (a G:C pair; 84 in total), to be replaced by a Z-DNA dimer unit.

I'm attaching a screenshot of the current structure, as well as the corresponding PDB file. I think Xiang-Jun might be able to work his "tasks" magic to align and insert the Z-DNA dimer units into the specified positions.

If you think this direction makes sense, I’d be happy to post the detailed process of how I constructed this circle.

87

RNA structures (DSSR) / Re: Rebuilding circular Z-DNA

« Last post by shr on April 23, 2025, 02:39:29 am »

My work focuses on molecular dynamics simulations of Z-DNA and its interactions with binding proteins. I'm particularly interested in understanding the mechanisms that stabilize Z-DNA, which is inherently less stable than B-DNA.
To explore this, I used the crystal structure of the ADAR1 protein bound to a short Z-DNA segment. Since the original segment was quite short, I wanted to extend the Z-DNA backbone. With your help, I was able to successfully simulate this extended structure. However, I encountered challenges in reproducing the specific protein–Z-DNA interactions observed in the crystal structure during my simulations. I believe this is due to multiple non-specific interactions forming between the DNA and the protein, which may mask or override the specific contacts I'm trying to study. It is not a Z-DNA remodeling problem but I am working on understanding Z-DNA stability.

In addition to Z-DNA, I also work on other non-canonical DNA structures, particularly G-quadruplexes (G4s). I’m developing a method to construct ideal G-quadruplex models from sequence data by first arranging guanine bases into tetrads, then building in the backbone and loop regions. As @Di_Liu suggested, I believe a similar model-building strategy could be applied to Z-DNA, to help generate consistent and realistic structures. What do you think about this approach or direction?

Thank you!

88

General discussions (Q&As) / Re: Rebuilding Z-DNA

« Last post by shr on April 23, 2025, 01:55:34 am »

I apologize once again. I look forward to the blogpost and will check out the thread "Rebuilding circular Z-DNA". I would be happy to contribute in any way I can.

89

RNA structures (DSSR) / Re: Can x3dna-dssr correctly handle N1-methyl-pseudouridine?

« Last post by xiangjun on April 22, 2025, 06:17:34 pm »

Hi Di,

Thanks for the detailed response. I can only wish that all users are just like you in providing such helpful feedback. Over the years, it is users like you who have motivated me to keep working on DSSR ...

Best regards,

Xiang-Jun

90

RNA structures (DSSR) / Re: Can x3dna-dssr correctly handle N1-methyl-pseudouridine?

« Last post by Di_Liu on April 22, 2025, 03:29:03 pm »

Hi Xiang-Jun,

Thank you for your detailed and insightful response. I'm truly impressed by your meticulous attention to details! It’s reassuring and strengthens my confidence in DSSR as a reliable tool!!! Also, thanks to your explanation and the referenced blog post, I now have a much clearer understanding of how the `--nt-mapping` option functions.​

I further tested `--nt-mapping`, and below is what I got:

Without `--nt-mapping`:

Code: [Select]

A.B8H7 has pseudo-uridine C1'...C5 glycosidic bond
B.B8H27 has pseudo-uridine C1'...C5 glycosidic bond
With `--nt-mapping='B8H:p'`, the result is the same as above, and the message reads:

Code: [Select]

uncommon base 'B8H' assigned to 'p' for A.B8H.7
uncommon base 'B8H' assigned to 'p' for B.B8H.27
A.B8H7 has pseudo-uridine C1'...C5 glycosidic bond
B.B8H27 has pseudo-uridine C1'...C5 glycosidic bond
With `--nt-mapping='B8H:u'`, I'm intentionally confusing the software to treat it as uridine, and I got the warning:

Code: [Select]

uncommon base 'B8H' assigned to 'u' for A.B8H.7
uncommon base 'B8H' assigned to 'u' for B.B8H.27
A.B8H7 has unusual GLYCOSIDIC bond!
B.B8H27 has unusual GLYCOSIDIC bond!
Best regards,

Di