Can DSSR detect nucleic acid ligand interaction

[lvelve0901]

Hi Xiangjun,

I am just curious whether DSSR can detect something like RNA and ligand/metal interaction in a PDB file.
For example, list all the hydrogen bond between RNA and ligand?

Best,
Honglue

[xiangjun]

list all the hydrogen bond between RNA and ligand?

Do you have a concrete example of such listing?

Xiang-Jun

[lvelve0901]

For example, in the dssr, there is a --get-hbond option. It will output all the H-bonds within two nucleotide and it gives you the distance, donor and acceptor etc., but I guess that only applies for nucleic acid. There is no way to detect H-bond between for example protein-and nucleic acid in current DSSR, right?

If not, do you have any suggestion of any software which can do something like parse the interactions between protein/peptide/ligand and nucleic acids.

Really appreciate your help.

Best,
Honglue

[xiangjun]

The DSSR --get-hbond option is more capable than it appears. In its default setting, DSSR only outputs H-bonds between nucleotides. Combined with the --json option, more H-bonds are avaible. Have a try and REPORT back if that fits your needs.

Of course, there are numerous other dedicated tools/resources you may find better-suited for your project.

Xiang-Jun

[lvelve0901]

Gotcha, I realized that Json file actually has what I need in the 'hbonds' section.

Also, is there also a section for metal in the pdb file. For example, how many metal-RNA interaction in the PDB file?

Best,
Honglue

[xiangjun]

Also, is there also a section for metal in the pdb file. For example, how many metal-RNA interaction in the PDB file?

Try the DSSR --metal option. Does that help?

Again, please REPORT back how it goes. Feedback makes the thread more complete and other viewers can benefit from our conversations.

Xiang-Jun

[lvelve0901]

Hi Xiangjun,

First, I want to apologize for not getting the feedback to you in time, though I carefully benchmarked the calculation as you suggested.

1. H-bond
For the H-bond between protein/peptide/ligand to nucleic acid, my target structure is 1PFE, which is a DNA bound to an antibiotic, echinomycin. I downloaded the biological assembly file and used the following command:

x3dna-dssr -i=1PFE.pdb -o=1PFE.json --json --more --symm

In the "hbonds" session of the output json file, I did found the all the DNA-drug interactions. For example,

{u'index': 31, u'atom2_serNum': 212, u'residue_pair': u'nt:aa', u'distance': 3.09, u'atom_pair': u'N:N', u'atom2_id': u'N@2:B.ALA6', u'donAcc_type': u'standard', u'atom1_id': u'N3@2:A.DG3', u'atom1_serNum': 69}

I have a few questions in terms of the hbonds output.

(1) How do I know which atom is H-bond donor and which is acceptor, like do you always put acceptor in the first place(atom1)?
(2) If the 'donAcc_type' is questionable, what does it mean? Does it mean that DSSR probably doesn't guess the valence properly?
(3) Generally speaking, for a random ligand (not peptide-linking or DNA/RNA-linking), how does DSSR guess the valence, like how to guess which heavy atom should be bonded to hydrogen?
(4) Wha does the 'serNum' mean here?

I am training a rotation student to use DSSR to parse all the drug and nucleic acid interactions from the entire PDB so hopefully we will keep updating the issues of DSSR hbonds under the same page.

--------------------------------------------------------------------------------

2. metal

I got a bit confused about your metal sessions in the json file.

My target structure is 1HR2. It is a P4P6 domain which has many Mg2+ in the coordinates.

I again downloaded the biological assembly file and tried to type:

x3dna-dssr -i=1HR2.pdb -o=1HR2.json --json --more --symm --metal

In the output json file, there is indeed a session called 'metals'. For example,

{u'index': 3, u'ligands_long': u'', u'num_ligands': 0, u'symbol': u'Mg', u'ligands_short': u'', u'id': u'A.MG55'}
{u'index': 4, u'ligands_long': u'A.A248,A.U249,A.G250', u'num_ligands': 3, u'symbol': u'Mg', u'ligands_short': u'AUG', u'id': u'A.MG57'}

In the index 3, I assume it means there is no residue/ligand interact with MG55 right? However, if you open the PDB file, don't you think that MG55 is very closed to the cytosine 255? I guess I might misunderstand something, so my questions in terms of metals are.

(1) How does DSSR define the interactions with metal involved?
(2) More generally, how doesn't DSSR define a metal. For example,

In the structure 1D8X, the COBALT HEXAMMINE(III) (NCO) which is a metal complex is considered as metal in DSSR.
In the structure 3MGV, the VANADATE ION (VO4) which is already an negative charged ion is considered as metal in DSSR.

Is there any list which DSSR think certain atom belongs to metal category?

--------------------------------------------------------------------------------

Again, I really appreciate your help with my research all the time and really hope DSSR will be better and better.

Thanks again.

Best,
Honglue

[xiangjun]

Hi Honglue,

This is a long list of questions, some of which are quite general. To proceed, please start a new thread for each related topic, illustrated with concrete examples.

As you know, some of DSSR features (like the --metal option) are experimental, and not documented yet. So you may be better off trying some other more polished (and published) tools/resources. For metal interactions with nucleic acids, for example, a quick online search immediately led to the following two papers:

• MINAS—a database of Metal Ions in Nucleic AcidS
• MeRNA: a database of metal ion binding sites in RNA structures.

For H-bonding detection, you may better try the well-established and published tools: HBPlus and HBexplore, as mentioned several times already.

Xiang-Jun