Building G-quadruplexes

[shr]

I am writing this code for GQ structure generation from sequence which can be found here https://github.com/sHr3y4s1/GQ-gen. I have just written this for the first G-track but this can be iterated to create more and then building in loops. I have attached an image of the output of this code. I don't know if this is the best way to do it but I am trying to create a basic canonical structure with specific topologies which can be energy minimized with an ion. I was thinking of a similar way for creating circular Z-DNA structures as well.

[xiangjun]

Hi shr,

I've split your response from the thread "Rebuilding circular Z-DNA" into its own thread for better organization and discussion.

It a nice start with the first G-tetrad. Please add more features to your GQ-gen.py script so it can at least build a complete G-quadruplex structure. I'll chime in with some suggestions to your project, while I'm working on adding proper Z-DNA backbone to DSSR-enabled models.

Best regards,

Xiang-Jun

[xiangjun]

Hi shr,

Following the discussion in the previous thread on "Rebuilding circular Z-DNA", as quoted below:

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.

I dug into the code of DSSR for modeling G-quadruplexes, and found the following experimental (and undocumented) features. DSSR can model G-quadruplexes using G-tetrad as the building block, and allows users to specify the number of G-tetrads and twist angle (among other things). See below for two examples: one with 3 layers of G-tetrads and 0 degrees of twist angle, and other with 6 layers and twist=36, respectively.

Best regards,

Xiang-Jun

[shr]

It looks like this can definitely be used as a building block. Is the DSSR code for G-Quadruplex open-source? If I may ask, would it be possible to look into the code? In my code, I tried to add more stacks but it seems a little tricky to do considering the backbone also needs to be bonded together.

With regards
Shreyasi Das

[xiangjun]

Hi,

Thanks for posting back and following up on the question about modeling G-quadruplexes. As mentioned in my May 05 post, G4 modeling are "experimental (and undocumented) features" in DSSR, and need to be further developed. DSSR is not open-source, and the Columbia Technologies Ventures (CTV) is in charge of licensing the command-line version of DSSR.

Best regards,

Xiang-Jun