3DNA citations from mainland Chinese researchers

Over the past couple of weeks, I have been quite surprised to notice the following four papers, by researchers from mainland China, that cite 3DNA:

• Feng et al. "Crystal structure of the crenarchaeal conserved chromatin protein Cren7 and double-stranded DNA complex." Protein Sci. 2010 Jun; 19(6):1253-7.
• Zhang et al. "Structural insights into the interaction of the crenarchaeal chromatin protein Cren7 with DNA." Mol Microbiol. 2010 Mar 16. [Epub ahead of print]
• Li et al. "Molecular dynamics studies of the 3D structure and planar ligand binding of a quadruplex dimer." J Mol Model. 2010 May 29. [Epub ahead of print]
• Chen et al. "Theoretical studies on the stacking interactions between methylated and unmethylated DNA bases." ACTA CHIMICA SINICA (in Chinese) 68(8):739-46. Published: Apr. 28, 2010.

For more ten years, this is the first time (to the best of my knowledge) that 3DNA has been cited by scientists from China, and it so happens that four come in a row. I am so happy to see that structural biology is shaping up in China. Surely, I would expect more 3DNA-citing papers from China to come in the following years.

block_atom, a little used 3DNA utility script

Following my previous post, "How is a base-pair rectangular block defined in 3DNA?", I feel it is in order to mention a tiny Perl script named block_atom that seems to have been little used by the 3DNA user community.

The basic idea of block_atom is to get an ALCHEMY data file which combines both atomic and block representations of nucleic-acid-containing structure in PDB format. The ALCHEMY file can then be displayed interactively using RasMol (v2.6.4, by its original author) (or Jmol).

Again, the point is best illustrated with an example. Here I am using 355d, the famous Drew-Dickerson B-DNA dodecamer solved at a high resolution by Williams and colleagues. Let the input PDB file be 355d.pdb, then the output file is automatically named 355d.alc, which can be displayed using RasMol with the options '-alchemy -noconnect'.

block_atom 355d.pdb
rasmol -alchemy -noconnect 355d.alc

One view of RasMol rendered image is as below, which shows more clearly the minor-groove (colored blue) of the DNA duplex and the various intra-base-pair deformations (e.g., propeller and buckle):
I initially wrote this utility script mostly for verification purpose, i.e., to make sure that the base reference frames are defined properly. For those who want to know more about 3DNA, having a look of the script (which is tiny) and understanding how it works could be a good exercise.

How is a base-pair rectangular block defined in 3DNA?

One of 3DNA's unique features is the base-pair (and base) rectangular blocks, as shown in the figure below. Since such a schematic was initialized by Calladine and Drew in their Understanding DNA book, I normally refer it as the Calladine-Drew style representation.


By default, a base-pair [BP, (a)] has a dimension of 10x4.5x0.5 Å; a purine [R, (b) left] 4.5x4.5x0.5 Å; a pyrimidine [Y, (b) right] 3x4.5x0.5 Å; and a mean base [M, (c)], which is exactly half of the base-pair, 5x4.5x0.5 Å.

The blocks are put into specific files: Block_BP.alc, Block_R.alc, and Block_Y.alc respectively. To use M for R and Y, one just needs to copy file Block_M.alc to overwrite Block_R.alc and Block_Y.alc in the current directory or the system directory ($X3DNA/config/). These blocks are used in the rebuilding and visualization components of 3DNA (see my blog post "blocview: a simple, effective visualization tool for nucleic acid structures").

The blocks are stored in the ALCHEMY format for easy specification of the nodes and edges, and since ALCHEMY is a format supported by RasMol (and Jmol). As an example, Block_BP.alc has the following content:

   12 ATOMS,    12 BONDS
    1 N      -2.2500   5.0000   0.2500
    2 N      -2.2500   0.5000   0.2500
    3 N      -2.2500   0.5000  -0.2500
    4 N      -2.2500   5.0000  -0.2500
    5 C       2.2500   3.5000   0.2500
    6 C       2.2500   0.5000   0.2500
    7 C       2.2500   0.5000  -0.2500
    8 C       2.2500   3.5000  -0.2500
    9 C      -2.2500   5.0000   0.2500
   10 C      -2.2500   0.5000   0.2500
   11 C      -2.2500   0.5000  -0.2500
   12 C      -2.2500   5.0000  -0.2500
    1     1     2
    2     2     3
    3     3     4
    4     4     1
    5     5     6
    6     6     7
    7     7     8
    8     5     8
    9     9     5
   10    10     6
   11    11     7
   12    12     8

Astute viewers may observe that nodes 1-4 are identified as N (nitrogen) and have exactly the same coordinates as 9-12 (C, carbon). This is a trick so RasMol can display the the minor groove edge in a different color than the other five sides of the rectangular, as shown in the following figure:

Note that the rectangular is preset in the standard base reference frame. Thus the nodes have y-coordinates of +5 Å and -5 Å along the long edge of the base pair, and x-coordinates of +2.25 Å and -2.25 Å along the short edge.

As an extra bonus of storing the blocks in external ALCHEMY text files, the dimensions of the blocks are be readily changed. For example, the depth of a block (z-coordinates) can be easily increased from 0.5 to 1.0 Å to make it thicker (see $X3DNA/config/Block_BP1.alc). Moreover, the blocks do not need to be rectangular either – see $X3DNA/config/block/Block_R_nr.alc for an example.

Naming conventions: RasMol, PyMOL and Jmol

Over the years, I've used the following three molecular graphics programs the most: RasMol, PyMOL and Jmol. It is interesting to note their different naming conventions: while their names all end with m-o-l (for molecule, I believe), the cases (used in convention) are different: Mol as in RasMol, MOL as in PyMOL, and mol as in Jmol.

For Jmol, there is actually an FAQ item "How do you write Jmol?" that reads "Capital J, lower case mol. Please do not write it any other way." For PyMOL, I am not aware of a specification on its name – I know that's the "official name" from its home page. Regarding RasMol, that's the most common way to name it, even though the title of its 1995 publication is "RASMOL: biomolecular graphics for all."

As for the prefix in the names, J in Jmol stands for Java; Py in PyMOL for Python; and Ras in RasMol could well be the initials of Roger A. Sayle, the original author of the program.

MODEL/ENDMDL records in PDB X-ray crystal structures

Over the years, I have always been using the PDB format for nucleic acid structures. Naturally I've thought that I know the format well, especially the "Coordinate Section." According to the PDB documentation,

MODEL/ENDMDL records are used only when more than one structure is presented in the entry, as is often the case with NMR entries.

In my experience, I have always connected the MODEL/ENDMDL pair only with the different models in an NMR entry. However, I was recently bitten by a subtlety in PDB format that is related to the MODEL/ENDMDL records in X-ray crystal structures which contain more than one asymmetric unit in their biological assembly.

As always, the point is best illustrated with an example – here I am using the four-stranded DNA Holliday junction X-ray crystal structure (1zf4/ud0061) solved by Ho and colleagues [PNAS 2005 May 17;102(20):7157-62]. As shown in the NDB website, the asymmetric unit of 1zf4/ud0061 contains only two chains; it is the biological assembly that has the four-stranded DNA junction.

I downloaded the biological assembly coordinates (in PDB format) from the NDB (named it '1zf4.pdb'), and ran blocview on it: blocview -i=1zf4.png 1zf4.pdb. However, the generated image [see Figure (A) below] has only half of what expected – as if the downloaded file contains only coordinates of an asymmetric unit. The mystery was gone when I checked the PDB file and realized that the MODEL/ENDMDL records now also apply to X-ray crystal structures to delineate symmetric-related units. Since 3DNA is designed to handle only one structure – it stops processing whenever an END or ENDMDL record is encountered. Simply change each 'ENDMDL' record to ' ENDMDL' (i.e., adding a space, or any character, for that matter) and run blocview again will get the expected image [Figure (B)].

Note that by default, RasMol also only displays the first model in a PDB file. To see multiple structures, the option '-nmrpdb' must be specified in the command line.

3DNA forum registration -- your id

Over the past couple of months, I have received a few emails with a subject line, as the title of this post, "3DNA forum registration -- your id". Presumably, such an email is from a (potential) 3DNA user, requesting for activation after 3DNA forum registration.

Clearly, "your id" should have been a specified user id. In a couple of cases, I tried to figure out the corresponding 3DNA forum ids based on email addresses and activated them. More recently, I've switched to ask the sender a very simple question: "So what is 'your id' specifically?" In at least two cases, I have never heard back from the original senders with 'your id' specified. To a certain extent, this is a surprising result: providing such information won't take more than a couple of minutes, and this will help me (and others) to help them better with 3DNA-related questions. I can certainly understand occasional negligence, but users must follow some common-sense rules. Thus those registrations are deleted, as junk ones, after some grace period.

The 3DNA forum is open to public for browsing, without registration. At its current settings, no emails are sent from the forum; do not confuse an online forum with a mailing list. You only need to register if you want (and are certainly more than welcome) to get more actively involved in, e.g. asking/answering questions, sharing tips/tricks with other users. These policies are enforced to make the 3DNA forum free from spams, as much as possible.

Some key combinations in MacBook Pro (Snow Leopard)

One of the inconveniences I experienced when first switching to a MacBook Pro running Mac OS X (Snow Leopard) was its missing of the PgUp, PgDn, Home and End keys. Over the past few months, I have learned that the functionality of such 'convenience' keys can be achieved via a combination of the arrow-keys (bottom right), with the 'fn', 'option', or 'command' keys (bottom left), as follows:

• fn + right-arrow – end of a document
• fn + left-arrow – beginning of a document
• fn + up-arrow – Page up
• fn + down-arrow – Page down
• command + right-arrow – beginning of a line (Home)
• command + left-arrow – end of a line (End)
• option + right-arrow – one word to the right
• option + left-arrow – one word to the left

According to Wikipedia, the 'fn' key "is a modifier key on many keyboards, especially on laptops, used in a compact layout to combine keys which are usually kept separate."

In addition to modifying cursor movements as noted above, the 'fn' key in Mac OS X can also be used to switch the default functionalities of F1 to F12 (e.g., F1 and F2 for screen brightness control) to the standard function keys. As an example, in MS Word, the keyboard shortcut for toggling case is "shift + f3", a trick I recently learned. In the default setting, one must press "fn + shift + f3" to achieve the desired effect.

Any tricks to share? I'd like to hear them!

One year of blogging

When I checked the date of my first blog post today, I was a bit surprised to find that it is exactly one year since I begin to blog on May 2, 2009. Altogether, I have written over 60 posts, slightly more than one per week. At this time, I feel it appropriate to summarize my thought on blogging in general, to provide a perspective to those who care to visit here and make comments.

• Why? The initial motivation was to use blog as a platform to express my personal views on issues I am interested in. As made clear in my first post, "this is Xiang-Jun's Corner on the Internet: all views are mine, and I am opinionated." Over the time, the blog posts have served as a convenient notebook (searchable and archived) either for my personal reference, or to refer others to a particular post (e.g., "On maintaining the 3DNA forum" when being asked a 3DNA-related question via email).
• What? "Random thoughts, mostly on scientific issues". I write only on issues I am familiar with and feel comfortable to say something, to the limit that I can respond quickly and concretely to users comments. I am always open to suggestions and will be prompt in acknowledging errors and making corrections. So far, the largest portion of the posts has been devoted to nucleic acid structures in general, and 3DNA-related topics in particular.
• How often? Due to time constraints, I will try to write one post per week at the minimum, maybe two, or in rare occasion three. Exceptions are possible, but by and large, I will aim for ~100 posts per year.
• Comment? Currently, the policy is set such that "Anyone - includes Anonymous Users" can make a comment, and the comments are moderated. So far, I have always approved all the comments as soon as I see them in my gmail alert, and follow up where appropriate. Note that due to global time difference, commenters may experience some lag in time.
• Does it work? Not unexpectedly, my blog has gradually attracted attentions from quite a broad audience, especially those interested in nucleic acid structures (3DNA), including leading scientists in the field (I know from emails I have received).
• Hot posts? According to Google Analytics, the most frequently visited nine posts are as follows (with posting date in parentheses):
  1. Curves+ vs 3DNA (Sunday, August 16, 2009)
  2. Does 3DNA work for RNA? (Friday, July 10, 2009)
  3. Two web-interfaces to 3DNA, and more (Sunday, July 5, 2009)
  4. Fit a least squares plane to a set of points (Saturday, August 22, 2009)
  5. Two 3DNA figures made into a textbook on structural biology (Sunday, May 3, 2009)
  6. Chemical diagram of Watson-Crick base-pairs (Saturday, January 23, 2010)
  7. What's special about the GpU dinucleotide platform? (Friday, April 2, 2010)
  8. Double helix groove width parameters from 3DNA (Saturday, September 5, 2009)
  9. How to calculate torsion angle? (Saturday, October 31, 2009)
  
  
  While some of the posts are well-expected to be in the list, a few of them (e.g., ls-plane fitting, calculation of torsion angle) could look a bit surprising. It does, however, verify an observation based on my personal experience and intuitive feeling about a technical niche that my expertise can make a difference.

Again, as I wrote in my first blog post, "Now the ball is rolling, and only time can tell where the destination will be -- but surely it will no longer stand where it was!" One year later, I can confidently say that the ball in rolling in the right direction, as I'd have hoped for. Of course, I know for sure more time and efforts are need to move to the next level, and I value your feedback!

Life is complicated -- is there a way to make it simpler?

To mark the 10th anniversary on completion of the draft sequence of human genome, the April 01, 2010 issue of Nature [464 (7289)] published a series of interesting and revealing articles, including an Editorial and (historical) accounts from Francis Collins and Craig Venter. I browsed through the whole list, and I especially liked the News article titled "Life is complicated" by Erika Check Hayden, a senior reporter for Nature. I was attracted by its catchy title and brief summary: "The more biologists look, the more complexity there seems to be. Erika Check Hayden asks if there's a way to make life simpler." Obviously, the title of this blog post was inspired by the sources.

Over the past decade, the Human Genome Project has helped to clarify the number of genes from previously assumed ~100,000 to the "true" number of only ~21,000. The dramatically reduced number of genes illustrates the crucial importance of non-coding (used to be called "junk") DNA to biology, yet what non-coding DNA does is still befuddling. Nowadays, we are faced with data deluge from sequencing, gene expression, protein (transcription factor) binding, and other new technologies. The complexity of biology has grown significantly, instead of simplified, even for the most extensively studied protein p53. As put by Jennifer Doudna, “The more we know, the more we realize there is to know.”

The community has gradually realized that information gathering does not always bring corresponding increase of meaningful biological insights. We are facing an age of “drowning in information, starved for knowledge.” For example, systems biology, a new discipline “supposed to help scientists make sense of the complexity”, has turned out that “In many cases, the models themselves quickly become so complex that they are unlikely to reveal insights about the system, degenerating instead into mazes of interactions that are simply exercises in cataloguing.” I cannot agree more with the comment by Leonid Kruglyak: it is naive to think that “you can simply take very large amounts of data and run a data-mining program and understand what is going on in a generic way.”

Are we lost in the sea of biological data? Not necessarily. Eric Davidson's work is an excellent example in “taking smarter systems approaches” to reveal overarching biological rules. Instead of a “machine learning” type top-down approach, the “insights have come when scientists systematically analyse the components of processes that are easily manipulated in the laboratory — largely in model organisms. They’re still using a systems approach, but focusing it through a more traditional, bottom–up lens.” Through this systemic bottom-up approach, Davidson's group has deciphered the mechanism of how gene expressions are controlled through regulatory interactions and specify the construction of sea-urchin’s skeleton.

Interestingly, Eric Davidson gave a seminar at C2B2 on Thursday, April 22, titled "Causal Systems Biology: the Sea Urchin Embryo Gene Regulatory Network". I was very impressed by his talk, and the points he made in the Nature News article.