Ed's Big Plans

Computing for Science and Awesome

Squishy TIM Barrel Subunits

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Again with the TIM Barrel pictures! Here’s some text about it from my notes…

1a5m (A Urease) is a really interesting protein– it consists of three subunits. Each subunit consists of three unique domains: a very squashed TIM Barrel, an alpha-alpha-alpha-beta-beta domain and a beta-beta-alpha-beta-beta domain. I’m not yet sure what to call little broken alpha helices that have less than two complete turns. The TIM Barrel (though exceedingly asymmetrical) will still be accounted for in the data to be analyzed. The TIM Barrel (566 amino acids) is the alpha subunit of each symmetrical subunit. The remaining two domains are the alpha and beta subunit though PDB is not clear which is which: they each weigh in at 100 and 101 amino acids. 1a5m is part of several solved urease structures in the PDB– the collection: {1A5K, 1A5L, 1A5M, 1A5N, 1A5O} are solved by Pearson et al. (1998).

Matthew A. Pearson, Ruth A. Schaller, Linda Overbye Michel, P. Andrew Karplus, and, Robert P. Hausinger (1998). Chemical Rescue of Klebsiella aerogenes Urease Variants Lacking the Carbamylated-Lysine Nickel Ligand. Biochemistry. 37(17):6214-20.

Squishy squishy shapes– the giant pink object in the next picture is actually three such TIM Barrels, each of which belongs to one of the three subunits.
Each of the three subunits are shown separately below…

1a5m_1_3 1a5m_2_3 1a5m_3_3

Aesthetically pleasing– these images were captured from the JMol output available from RCSB PDB.

Eddie Ma

October 14th, 2009 at 9:49 am

TIM Barrels look like this…

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It occurred to me that I didn’t actually post any images in the past few posts. Here are two TIM Barrels that I’ve arbitrarily picked from DATE. Note– the image files are horribly misnamed, so please use the text description underneath.

From left to right– these figures are 1A53 (Beta Strand C-Face), 1A53 (Beta Strand N-Face), 1BG4 (Beta Strand N-Face), 1BG4 (Beta Strand C-Face). 1A53 is called “indole-3-glycerol phosphate synthase” and 1BG4 is called “xylanase” isolated from Penicillium simplicissimum. I won’t go into the function of each of these enzymes, but they do illustrate what a general beta-alpha TIM barrel looks like. TIM Barrels comprise of eight beta-alpha secondary structure elements. Extra helices and sheets may occur but must flank the TIM Barrel-like portion of the protein domain (1A53 has a very prominent extra alpha helix close to the camera in the far left image). The “barrel” name derives from the twisted cylinder enclosed by the parallel beta sheets in the middle of the object. TIM barrels can be deformed quite a bit too if they’re a subunit part of a larger holoprotein.

The four-character designations (1A53, 1BG4) are RCSB (A Resource for Studying Biological Macromolecules) Protein Data Bank identifiers– I’ve found that SCOP frequently links into PDB while PFAM frequently links to UniProtKB (Knowledge Base) and utilizes UniprotKB identifiers. More on that later…

Eddie Ma

October 6th, 2009 at 10:52 am

TIM Barrels and 4-Alpha Helix Bundles

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Beta-Alpha TIM Barrels and 4-Alpha Helix bundles are the first of the major folds I’ll be looking at here at Waterloo…

As with all academic projects, the probability of goal, approach and method mutation is high. Looking at the above protein folds serves as an excellent starting point as I’ll be applying some of the established methods that Andrew and Aaron have developed.

Alpha helices and Beta sheets are objects that any highschool biologist is acquainted with. To recapitulate, alpha helices are sequences of amino acids arranged so that the alpha carbon of each amino acid falls along the path of a helix. The number of amino acids per turn in this peptide and the regularity of the helix are determined by both the sequence and the environment that peptide finds itself in. Amino acids in the beta sheet conformation are arranged so that their alpha carbons zig zag. The result is a nice wide and flat shape schematically drawn as a sheet. Alpha helices and Beta sheets are collectively called secondary structural elements.

So, folds are these giant overarching classification of proteins– Folds themselves are inherently structural, so classifying them OR using them as classifications is only relevant in structural studies and databases on the web like SCOP and CATH. In databases such as SCOP and CATH, classification of similarly structured proteins start by determining whether the protein contains mostly alpha helices; mostly beta sheets; beta sheet and alpha helices alternatively and irregularly; or beta sheet and alpha helices in distinct regions of a protein. In SCOP, further classification is done by manually assigning proteins to smaller and smaller categories, while in CATH, these classifications are done by a hidden Markov model and then manually inspected (or not). It turns out that CATH uses a similar manual approach, and uses HMMs only to assist; contrast with PFAM which actually utilizes HMMs for the majority of work and is verified afterward by humans.

Certain folds like the beta-Trefoil and TIM Barrel benefit from containing only proteins that cleanly fit into some subcategory or several subcategories– it is then possible to just drill into the right level of categorization and pull out all of the beta-Trefoils and TIM Barrels we want.

The 4-Alpha-Helix Bundle constitutes a fold of protein that manages to be spread around the databases, being a very common secondary structural repeat; also a very small repeat when compared to the two giants above. These two items represent an interesting contrast too. Both machine and human intelligence pulls TIM Barrels together while sprinkling alpha-helix bundles across databases and subcategories. And yes, the size difference helps too.

So, I’m starting with a structural then sequence based alignment for single domain TIM Barrels and alpha-helix bundles; to be completely focused, an objective is named: To identify where sequence repeats occur in each individual protein.

Eddie Ma

September 24th, 2009 at 2:09 pm

New Diagram for MSc-X3 (math paper)

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Brief: I’m particularly happy with this diagram… I had something along these lines in my head for a while, but I never could figure out how to draw it correctly. I never thought that simplifying it to three easy steps was the smarter thing to do.

Some Assembly Required.

Eddie Ma

August 20th, 2009 at 12:08 pm

Monet Molecules c/o Autotrace

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A Monet Isopentenol c/o Autotrace

A Monet Isopentenol c/o Autotrace

Brief: Happy accidents make me happy– here’s isopentenol after grabbing it as an SDF out of PubChem, dumping it out into a PNG with Bioclipse, grayscaling it with GIMP— then converting it to an SVG with Autotrace (RO IT Systems)… It’s just pretty… like a Monet. Of course, I have to go back and make it look like a molecule again for a paper… but I’m going to admire the pretty little alcohol for a bit.

Eddie Ma

July 9th, 2009 at 2:56 pm

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