Can 3DNA DSSR handle Left-handed DNA?

[GengshiWu]

Dear Xiang-Jun,

Our lab is currently studying left-handed DNA (L-DNA). I’d like to clarify that by L-DNA we mean the mirror image of standard B-DNA, rather than the L-DNA fiber model included in the 3DNA DSSR library.

Specifically, our structure (b40-rb10.5_out_minimized_aligned2Z_i_x.pdb) was generated by applying a mirror transformation to a standard B-DNA model (b40-rb10.5_out_minimized_aligned2Z.pdb) that we constructed using the DSSR fiber B-DNA model but with modified parameters for 10.5 bp/turn.

When we analyzed this mirror-image L-DNA with x3dna-dssr analyze, the program successfully identified the helix start and end points (as shown in the attached image), but the helix form was not recognized as L-DNA.

My questions are:

1. Is my understanding correct that DSSR can identify the geometry but does not recognize the form of our L-DNA?

2. Is there any way to make DSSR recognize the form of our L-DNA?

Thank you for your time and and for updating this excellent tool!
I also attached the two files mentioned above

Gengshi Wu

[xiangjun]

Hi Gengshi,

Thank you for sharing details about your L-DNA structure (mirror image of standard B-DNA). It seems to represent a novel form, and I plan to investigate it further. If feasible, I will update DSSR to accommodate this new form.

Best regards,

Xiang-Jun

[xiangjun]

Hi Gengshi,

I've checked the two PDB files you uploaded: a standard B-DNA model (ending with aligned2Z.pdb), and its mirror-image (L-DNA), with x-coordinates negated (ending with aligned2Z_i_x.pdb). For clarity, I've extracted the first 6 atoms from each file, so readers easily see the differences.

# a standard B-DNA model          x
ATOM      1  P    DA A   1       0.621   9.421  -1.028  1.00  0.00           P
ATOM      2  O1P  DA A   1       0.606  10.783  -1.583  1.00  0.00           O
ATOM      3  O2P  DA A   1       1.439   9.186   0.166  1.00  0.00           O
ATOM      4  O5'  DA A   1      -0.863   8.945  -0.676  1.00  0.00           O
ATOM      5  C5'  DA A   1      -1.693   8.405  -1.689  1.00  0.00           C
ATOM      6  C4'  DA A   1      -2.528   7.255  -1.154  1.00  0.00           C

# a mirror-image, with x-coordinates negated
ATOM      1  P    DA A   1      -0.621   9.421  -1.028  1.00  0.00           P
ATOM      2  O1P  DA A   1      -0.606  10.783  -1.583  1.00  0.00           O
ATOM      3  O2P  DA A   1      -1.439   9.186   0.166  1.00  0.00           O
ATOM      4  O5'  DA A   1       0.863   8.945  -0.676  1.00  0.00           O
ATOM      5  C5'  DA A   1       1.693   8.405  -1.689  1.00  0.00           C
ATOM      6  C4'  DA A   1       2.528   7.255  -1.154  1.00  0.00           C

Mathematically, this is a simple operation, but you have created a hypothetical DNA type that is unknown to DSSR. Nevertheless, DSSR is functioning as intended:

• For the standard B-DNA model, DSSR classifies the dinucleotide step as 'B' correctly.
• For the L-DNA, DSSR cannot classify the dinucleotide steps. and designates them as '.' (see the section below). Also as noted in the header section, DSSR only recognizes the common A-, B-, and Z-form helices.

  Note: a helix is defined by base-stacking interactions, regardless of bp
        type and backbone connectivity, and may contain more than one stem.
      helix#number[stems-contained] bps=number-of-base-pairs in the helix
      bp-type: '|' for a canonical WC/wobble pair, '.' otherwise
      helix-form: classification of a dinucleotide step comprising the bp
        above the given designation and the bp that follows it. Types
        include 'A', 'B' or 'Z' for the common A-, B- and Z-form helices,
        '.' for an unclassified step, and 'x' for a step without a
        continuous backbone.
      --------------------------------------------------------------------
  helix#1[1] bps=40
      strand-1 5'-AAAAAAAAAATTTTTTTTTTCCCCCCCCCCGGGGGGGGGG-3'
       bp-type    ||||||||||||||||||||||||||||||||||||||||
      strand-2 3'-TTTTTTTTTTAAAAAAAAAAGGGGGGGGGGCCCCCCCCCC-5'
      helix-form  .......................................

1. Is my understanding correct that DSSR can identify the geometry but does not recognize the form of our L-DNA?

Yes, that is correct. DSSR can see this is a left-handed helix, but it (currently) does not recognize your L-DNA form.

Along the line, one could imagine another form where y-coordinates are flipped. What would it be called? How would DSSR suppose to classify it?

2. Is there any way to make DSSR recognize the form of our L-DNA?

In principle, yes. One just needs to incorporate the domain-specific knowledge into the DSSR code. I need to know more about your L-DNA before considering how to do that.

Best regards,

Xiang-Jun