Identification of C-H...N/O H-honds using 3DNA

Recently, I came across an interesting article by Kiliszek et al., titled "Atomic resolution structure of CAG RNA repeats: structural insights and implications for the trinucleotide repeat expansion diseases". In addition to its biological implications, this paper uses 3DNA to deal with non-canonical-base-pair-containing helical structures in a sensible way:

The helical parameters were calculated using 3DNA (29). Sequence-independent measures were used, based on vectors connecting the C1' atoms of the paired residues, to avoid computational artefacts arising from non-canonical base pairing.

Another significant point, which is the focus of this post, is the observation that "All the adenosines are in the anti-conformation and the only interaction within each A-A pair is a single C2-H2...N1 hydrogen bond." (Figure below) Given the 0.95 Å ultrahigh resolution of structure 3nj6/na0608, it is likely that this type of A-A is real.


The find_pair program in the currently distributed versions of 3DNA (v2.0 and before), however, does not identify this A-A pair (thus the corresponding NDB list of "Base Pair Step Parameters" is incomplete) for the following two reasons:

1. No H-bond exists between N/O base atoms – currently a requirement for a base-pair.
2. By default, only N/O atoms are used in defining H-bonds (see tag hb_atoms in file "misc_3dna.par"). Nevertheless, by adding C as a possible atom in forming H-bond, and manually editing find_pair generated input file to analyze, 3DNA structural parameters can be calculated as usual.
   

I have updated find_pair in 3DNA to identify such C-H...N/O H-bond automatically (see below for entry 3nj6). Upon further refinements and validations, future releases of 3DNA will have this functionality available.

    1   95  #    1 | ...1>A:...1_:[..G]G-----C[..C]:..10_:A<...2
    2   94  #    2 | ...1>A:...2_:[..G]G-----C[..C]:...9_:A<...2
    3   93  #    3 | ...1>A:...3_:[..C]C-----G[..G]:...8_:A<...2
    4   92  #    4 | ...1>A:...4_:[..A]A-**--A[..A]:...7_:A<...2
    5   91  #    5 | ...1>A:...5_:[..G]G-----C[..C]:...6_:A<...2
    6   90  #    6 | ...1>A:...6_:[..C]C-----G[..G]:...5_:A<...2
    7   89  #    7 | ...1>A:...7_:[..A]A-**--A[..A]:...4_:A<...2
    8   88  #    8 | ...1>A:...8_:[..G]G-----C[..C]:...3_:A<...2
    9   87  #    9 | ...1>A:...9_:[..C]C-----G[..G]:...2_:A<...2
   10   86  #   10 | ...1>A:..10_:[..C]C-----G[..G]:...1_:A<...2
##### Criteria: 4.00  0.00  15.00  2.50  65.00  4.50  7.50   [ O N C]
##### 2 non-Watson-Crick base-pairs, and 1 helix (0 isolated bps)
##### Helix #1 (10): 1 - 10

The Jmol paper: a paradigm shift in crystallographic visualization

From the Jmol mailing list, I noticed Prof. Robert Hanson's announcement titled "Jmol and crystallography: the paper". Finally, an "official" paper has been published on Jmol, an increasing popular molecular visualization tool.

While the paper is categorized under "teaching and education" and summarized as below:

Recent advances in molecular and crystallographic visualization methods are allowing instructors unprecedented opportunities to enhance student learning using virtual models within a familiar web-browser context. In step with these advances, the latest versions of the Jmol molecular visualization applet offer capabilities that hold potential for revolutionizing the way students learn about symmetry, uncertainty and the overall enterprise of molecular structure determination.

Jmol is certainly as useful for research as other commonly used molecular visualization tools, such as PyMOL and RasMol. Specifically, Jmol applets have become dominated in web-based applications/resources (including RCSB PDB). In fact, the HTML version of the paper itself makes extensive use of Jmol applet for interactive manipulation of over 20 figures.

Over the past couple of years, I have witnessed the many new features added to Jmol, driven by an active and friendly user community. I have been particularly impressed by Prof. Hanson's quick and to-the-point responses to users' requests for new features and bug reports, including to my request for Jmol's "Support of 'alchemy' format for rectangular schematic base-pair geometry". Overall, the paper presents a nice overview of some of Jmol's new functionality, and could become highly cited.

Reading through the paper, I was just a bit surprised that PyMOL is not mentioned. Nowadays, Jmol and PyMOL are apparently the top two molecular graphics software tools, with common and complementary functionality.