search

moritzobenauer / ProjectRaccoon

Automated construction of atomistic and coarse-grained models in the PDB format for polymer peptide conjugates.
GNU General Public License v3.0
5 stars 1 forks source link

Petition for another feature: allow adding nucleotides when elongating a linear chain #15

Open taoliu032 opened 6 months ago

taoliu032 commented 6 months ago

Hello!

Thanks for developing this nice piece of software! I wonder if it is interesting for the developers to include nucleotides (DNA or RNA) into the monomer scope so that one can use ProjectRaccoon to create polymer-nucleic acid conjugates? This type of conjugates have also been showing lots of exposure in literature, in part because of the high density of negative charges carried by nucleotides. They can be made of (1) nucleotides only (with or without chemical modifications), or (2) nucleotide-polymer conjugates.

Based on the current workflow, I think adding nucleotides as building blocks seems like a low-hanging fruit, yet can certainly benefit a larger community :)

Happy to discuss more!

moritzobenauer commented 6 months ago

Dear @taoliu032 ,

thank you for that very interesting idea. We will definitely have a look at this. I have never studied nucleotide-polymer conjugates before: can you recommend a good review article describing the binding motifs between nucleotides and polymers?

Adding the nucleotide bases as building blocks is something we will have a look at in the upcoming weeks. However, I have not worked with DNA/RNA before: as far as I am aware the capping (at least for mRNA) is done with Methylguanosine and poly-A on the other side. You may already know of a review paper describing the computational modeling of nucleotides.

Again, thank you for your input. Looking forward to work on that.

Best, Moritz

taoliu032 commented 6 months ago

Hi @moritzobenauer, thanks for being interested!

I am no expert in such kind of conjugates either, but what I had seen in literature either covalently or ionically link together nucleotide and polymer. There is more than one type of covalent linkage people have tried: Here are two examples: Figure 1A in https://doi.org/10.1016/j.chempr.2021.05.022, and Figure 4 in https://doi.org/10.1021/bc000010p.

I have worked with DNA molecules and used conventional Amber14 force field (OL15 force field) to model all-atom models. Although force fields for nucleic acids are in general not as well developed as those for proteins. And I don't think it is necessary to cap DNA in the nucleotide-polymer conjugate application. For example, in the first example, a sequence they used was: [polymer]-TTTTTCAGTTGACCATATA. For RNA, capping may be necessary to reduce its reactivity for better stability. Here is a nice review (a bit old though): https://doi.org/10.1016/j.sbi.2012.03.012

Hope these can help!