1h1k secondary structure

[erikbike]

I am trying to understand the secondary structure for PDB 1h1k [whole chain].  This is a series of A's followed by U's.  When I compute the structure with DSSR, it looks something like:

((([[[{{{)))]]]}}}

I think that this indicates there is a pseudo-knot.

If the option --nest is added, the structure looks something like:

(((....)))....

I expected the structure in both cases to look something like:

(((((())))))

I suspect that this has something to do with the fact that the structure is split into multiple chains.

The actual outputs are attached.  I am using DSSR v1.2.6-2015mar28.

I would appreciate if the structures could be explained, so that I can better understand the outputs in this case.

Thanks, Erik

[xiangjun]

Hi Erik,

Thanks for trying out DSSR and posting your questions on the Forum. Regarding the issue you experienced, please see my blog post, "DSSR-derived DBN for an input entry with multiple RNA molecules", and the notes therein. The most relevant part is quoted below:

The issue on proper ordering of multiple chains to avoid crossing lines (false pseudoknots) has been formally addressed by Dirks et al. in their 2007 article titled Thermodynamic analysis of interacting nucleic acid strands (SIAM Rev, 49, 65-88), specifically in Section 2.1 (Fig. 2.1). Applying that algorithm to nucleic acid structures, however, is beyond the scope of DSSR. The program strictly respects the ordering of chains and nucleotides within a given PDB or PDBx/mmCIF file, but outputs warning messages where necessary to draw users’ attention. As another example, I’ve recently noticed that DNA duplexes produced by Maestro (a product of Schrödinger) list nucleotides of the complementary strand in 3′ to 5′ order to match the 5′ to 3′ directionality of the leading strand for each Watson-Crick pair (See below).

For the case of 1h1k, please note the following sections from DSSR output:

Code: [Select]

File name: 1h1k.pdb
    no. of DNA/RNA chains: 6 [I=412,J=276,K=265,L=412,M=276,N=265]
    no. of nucleotides:    1906
    no. of atoms:          40008
    no. of waters:         0
    no. of metals:         0
and

Code: [Select]

****************************************************************************
Special notes:
   o cross-paired segments in separate chains, be *careful* with .dbn

****************************************************************************
This structure contains *2-order pseudoknot
   o You may want to run DSSR again with the '--nested' option which removes
     pseudoknots to get a fully nested secondary structure representation.
   o The DSSR-derived dbn may be problematic (see notes above).
HTH,

Xiang-Jun

[erikbike]

Hi Xiang-Jun,

Thank you for the thorough reply.

One related question:  When specifying --nest, is this equivalent to replacing all {}, <>, etc. with "." in the DBN?  Or does --nest do something more complicated?

Thanks again,
Erik

[xiangjun]

When specifying --nest, is this equivalent to replacing all {}, <>, etc. with "." in the DBN?

Yes. That's why if the original DBN is problematic, then the nested version would be meaningless.

DSSR could be "smarter" by checking/rearranging chains order, among many other things. I decided to remain simple and made DSSR follow strictly what's in the input PDB or PDBx/mmCIF file. This way, if anything goes wrong, it is easy to identify where the problem is, as shown clearly in your case.

Best regards,

-- Xiang-Jun