Catalytic Antibodies Simply Explained
Posted 1:17 AM

Catalysis is the process of speeding up a chemical reaction by lowering its activation energy - the energy hump a reaction has to go over before it can roll downhill. Efficient catalysts of chemical reactions are extremely commercially valuable and widely researched.

Enzyme Catalysis Basics: Biological enzymes are known to catalyze (speed up) chemical reactions, in part, by stabilizing the transition state (halfway point at the top of the hump) of an otherwise energetically-favorable (downhill) reaction. Some catalysts work by moving chemicals next to each other that would otherwise not randomly meet that often. (1) Some enzymes are known to change their shape (conformation) after binding and during the reaction - driving catalysis (2).

The immune system can be stimulated to respond to a incredibly diverse range of molecules by producing antibodies which bind (cling, stick) to these molecules. The theory of "catalytic antibodies" was that if an antibody was purified that bound to the transition state of a reaction, it would, in the same manner as an enzyme (above), stabilize that state (drag it up the hill) and accelerate the reaction. In order to generate such an antibody, a "transitions state analog" (TSA) - molecule that looks like the known transition state of a reaction - is used. Antibodies that are generated (usually by injection into a mouse) to bind to that TSA are then screened until one is found that catalyzes the reaction. Surprisingly, to me, this works very well. (3)

However, these "abzyme" catalysts are never as efficient as enzymes for many reasons. The abzyme may strongly bind to the product of the reaction (not letting go when it's done), greatly inhibiting its effectiveness. Also there is the difficulty of creating a TSA - they may differ in bond angles or polarity, etc. Many enzymes form strong (covalent) bonds during their catalysis mechanism, but this is not known to be possible with abzymes. Enzymes also employ conformational changes, metals and other cofactors to accelerate catalysis.

Abzymes are being aggressively researched, however. For example, it may be possible to engineer abzymes which bind to prosthetic groups to be used in metal-catalyzed reactions. Abzyme reactions which employ several cofactors have already been demonstrated. (4,5)

(1) "Chemical basis for enzyme catalysis", 2000, TC Bruice, SJ Benkovic
(2) "Catalysis by Enzyme Conformational Change", 2004 Jiali Gao1, Kyoungrim Lee Byun, and Ronald Kluger
(3) "Catalytic antibodies" (Biochem. J.), 1989, G. Michael BLACKBURN,t Angray S. KANG
(4) "Pyridoxal 5?-Phosphate-dependent Catalytic Antibody" (1996) Svetlana I. Gramatikova, Philipp Christen
(5) "A cofactor approach to copper-dependent catalytic antibodies" Kenneth M. Nicholas, Paul Wentworth, Jr

Labels: biotech

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Nofollow, Viagra, Google & I told You So
Posted 8:05 AM

When someone links to a website, Google and other search engines have, in the past, considered that a "vote" of confidence for the site linked to. The higher reputation a site has, the more it's vote counts... (sort of, there's lots of other factors).

The idea behind "nofollow" is that you can link to a site, but also mark it as "I'm not voting for it". That way someone who has, for example, a list of comments on their blog, won't simply "vote" for everyone who posts a comment. Presumably that would prevent spammers from posting a million comments in the hopes of getting their discount Viagra ad's search ranking up.

It's a solid concept, but in practice it has backfired because it was coupled with a "punishment" system for linking to spam sites.

This punishment system has led sites like Wikipedia, which are, for the most part, extremely reputable, to put "nofollow" on every single link in an attempt to prevent spam. These links are, usually, extremely well-vetted votes of confidence for the site in question. Wikipedia, despite its problems, remains one of the foremost authorities on "link quality".

Other quality sites that have adopted "nofollow" on every link include Digg and Twitter.

You see where this is going. Rather than rely on top authorities with quality information, like Wikipedia, Digg, etc. Google now has to rely only on links originating from people who don't know or care about their link voting/ranking, etc. In other words, generally less knowledgeable or lower quality votes are the only votes used for ranking.

This ultimately harms Google's page ranking system. What Google needs to learn is that "open" is not the right way to go for search rankings. Heavy use of personalized and regional results is the only thing they've done to halt this trend. Here's the next step: allow someone to mark another Google user as "trusted" for search results. In other words, I should be able to mark friends of mine as "trusted" (on a scale of 1 to 5 maybe), for personalized search results.

That way personalization will dominate the results, be highly relevant, and impossible to game.

Google, the last time I emailed told you to track clicks you listened...and it helped. But you never thanked me! Get back to me when this multilevel personalized trust system is done.

Labels: google

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Myoglobin Pov-Ray
Posted 9:34 AM

One of my assignments from biochem class was to play around with VMD and Pov-Ray. It was fun. The red sphere is supposed to be an oxygen.... (I know it's not that big, or shiny, or red and there's no heme prosthetic to bind it with.)

You can click on the image to zoom in.

Labels: biotech

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