Modified nucleotides in the PDB

In addition to the five canonical bases (A, C, G, T, and U), nucleic acid structures in the PDB contains numerous modified variants (natural or engineered) in the nucleobase, sugar, or the phosphate. For instance, the 76-nt (nucleotide) long yeast phenylalanine tRNA (1ehz) contains 14 modified bases: 2MG10, H2U16, H2U17, M2G26, OMC32, OMG34, YYG37, PSU39, 5MC40, 7MG46, 5MC49, 5MU54, PSU55, and 1MA58. Among which, the most prevalent and best-known example is pseudouridine. Note that in the PDB, each residue (including modified nt) is named with an up to three-letter identifier, e.g., PSU for pseudouridine. For a comprehensive list (with chemical and structural information) of small molecules, including modified nts, please refer to the Ligand Expo website hosted by the RCSB PDB.

Given the widespread occurrences of modified bases in nucleic acid structures, any practical structural bioinformatics software should be able to treat them effectively, as with the canonical bases. In 3DNA, from the very beginning, modified bases are mapped to standard counterparts, e.g. 5‐iodouracil (5IU) to uracil (U) and 1‐methyladenine (1MA) to adenine (A), allowing for easy analysis of unusual DNA and RNA structures (see the NAR03 reference). Specifically, in the 3DNA distribution the file baselist.dat contains the mappings explicitly.

As of v2.1, 3DNA automatically maps a new modified base not available in the file baselist.dat. Yet, I have continuously updated the list in line with new DNA/RNA entries released by the PDB. The process is automated with a Ruby script which calls find_pair -s on each nucleic-acid-containing structure to output unknown bases. As an extreme, the baselist.dat file below comprises only canonical bases:

  A   A
  C   C
  G   G
  T   T
  U   U
 DA   A
 DC   C
 DG   G
 DT   T

With the above minimum mapping list, running the command find_pair -s on 1ehz.pdb identifies all the 14 modified bases. A sample case for 2MG is shown below:

Match '2MG' to 'g' for residue 2MG   10  on chain A [#10]
    check it & consider to add line '2MG     g' to file <baselist.dat>

By parsing the output of a batch run on all DNA/RNA-containing entries in the PDB as of October 18, 2013, I identified a total of 596 modified bases. The top portion is as below:

02I     a
08Q     c
08T     a
0AD     g
 0C     c
0DC     c
0DG     g
0DT     t
 0G     g
0KL     u
0KX     c
0KZ     t

An explicit list of base mapping makes the correspondence transparent, and helps avoid ambiguous cases as to which canonical base a modified nt matches to. DSSR uses the same list internally. Hopefully, the information would also be useful to other related projects.

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