Wednesday, February 25, 2009

ATP-Synthase Modeled in Glass

The Medical Museion at the University of Copenhagen has this interesting sculpture of ATP-Synthase entirely in glass. Take a look at their site. Scroll down to the comments where the artist, Colin Rennie, shares some of his thoughts on the scuplture.  It's difficult to really see what it looks like from the photos. I would love to got there to see it myself.

ATP-Synthase is the enzyme responsible for making most of the ATP formed in cells - the main form of stored cellular "energy."  The sculpture is based on a crystal structure published in 1999 and available at the Protien Data Bank, PDB ID 1QO1.

By way of

Tuesday, February 24, 2009

Tycho's Supernova

In 1572, the Danish nobleman Tycho Brahe observed a "new star" in the sky in the constellation Cassiopeia.  He published a small book on his observations of this new star called "De Nova Stella," and thus coined the term nova.  We now know that Tycho's star was actually a supernova and it is still being studied today. Both novae and supernovae involve explosions by stars that cause them to become much brighter than normal.

This is a composite image from NASA's Chandra X-ray Observatory and the Spitzer Space Telescope.  The green and yellow are from x-rays emitted by the expanding shell of gas from the original explosion more than 400 years ago.  The blue represents the shock wave from the explosion, also from x-ray emissions.  The red is dust observed in infrared wavelengths.

You can get this image and more from the Chandra Observatory's web site.  There are desktop patterns and wallpapers in several sizes, and a lot of other cool stuff.  Take a look at the photo album for more details about this image.

Science Careers Booklet from AAAS

The Association for the Advancement of Science (AAAS), publishers of Science magazine, have put together a booklet of advice for people planning on a career in science.  There are chapters on graduate school, skills for scientists, resumes and networking, non-traditional careers, diversity issues and others.

The articles were originally written for their careers web site and have been collected into an 88-page booklet.  You can see the original articles, individual chapters, or download the whole booklet as a PDF file.  And it's FREE.

Career Basics Booklet - Biotech, Pharmaceutical, Faculty, Postdoc jobs on Science Careers

Saturday, February 21, 2009

Musical Interlude from Venezuela

Gustavo Dudamel and the Teresa Carreño Youth Orchestra

From this year's Ted conference.  These are high-school aged kids and absolutely incredible. 

Monday, February 16, 2009

Viewing 3D Structures at PubChem

PubChem is now providing 3D structures which you can view or download.  PubChem3D generates a single conformer for molecules which are not too large or too flexible.  You can view the results of this on the compound summary pages.  The Compound Summary page shows the structure of the compound with two tabs at the top: you can choose either the customary 2D view, or a 3D image by clicking the appropriate tab.

You also have the option of an interactive view by clicking either the tetrahedral molecule icon
or the image of the 3D molecule.  There are two options for viewing the molecule.

The first is a web-based viewer that opens a new window and generates an animated gif on the fly.  This web-based viewer takes a little getting used to, and strikes me as rather clumsy.  I don't understand why they did not use a java applet such as Jmol instead.  In fact, Rajarshi Guha's Pub3D site does just this.  Enter a PubChem cid and you can see the 3d structure using Jmol.

The second option for viewing the structure in 3D is to download and install the PubChem 3D Viewer. Windows, Linux and Mac versions are available.  The graphics are nice, but it is limited to the file formats used by PubChem: pc3d, asn,  and sdf for multiple molecule files.  You can load more than one molecule at a time by either opening a multi-molecule sdf file or using the Import option.  With more than one molecule loaded you can toggle between a panel-view which displays all the molecules in a table format, or an overlay mode.  Select which molecules to overlay in the Molecules tab in the right-hand panel.

In addition, the right-hand panel has controls for changing the way the molecule(s) are displayed. Oddly there is no Save function.  There might be no particular need to save the molecular data files from the viewer, but they seem to have gone to some trouble to give a lot of graphics display options.  It's too bad that you cannot save images from the PubChem 3D Viewer.

Saturday, February 14, 2009

Kodo Drummers!

We saw Kodo last night in Ann Arbor. You really have experience Kodo in person, but this clip gives you a sense of their power and precision.

Tuesday, February 10, 2009

Create a Chemical-Free Dryer Satchel ... and Be Sure to Proofread Carefully has a link to a Do It Yourself site for making a sachet you can put in the clothes dryer to make your clothes smell nice.  This one is fun to read just for the comments that other readers have left.  Several point out in amusing ways the absurdity of anything being "Chemical-Free." It's nice to know I'm not the only person out there who is annoyed by such willful ignorance.

Some of the other comments suggest that you probably want to make a "sachet," and not a "satchel" for this project as the Lifehacker title puts it.  This would probably make a big difference in terms of the cost and effectiveness of the project.

In response to the article's suggestion that minty-smelling sheets would be pleasant, one commenter says, "If my sheets smelled like mint, I would probably eat them in my sleep."

Take a look for yourself, and be sure to read the comments too.

DIY: Create a Chemical-Free Dryer Satchel

Sunday, February 8, 2009

CN7 - An Anion that Goes Boom

How could I pass up reading this article when the abstract had a picture of an explosion? But seriously, the molecule is cool and has an interesting structure.

The tetrazole ring looks like it ought to be aromatic. It resembles pyrrole: a five-membered ring with two double bonds and a lone pair on the NH nitrogen so you would think it would be aromatic. In addition, the tetrazolate anion is typically written with an aromatic symbolism having a circle inside the ring rather than showing double and single bonds.

The tetrazole ring itself is used in biological chemistry because it is acidic like a carboxylate group but it will not do the same reactions as a carboxylate, like form amide or ester bonds. In designing drugs, a carboxylate can be replaced with a tetrazole group. It is roughly the same size and will have a negative charge like a carboxylate, but since it cannot react chemically like a carboxylate it can get stuck without reacting and thus serve as an inhibitor.

Of course that is not what the present authors are interested in. They like the fact that it blows up. Be reassured, not all tetrazole compounds are explosive, especially not those used in the pharmaceutical industry.

In this paper, the authors react CHN7 with different bases to prepare a number of different salts of the CN7 anion paired with different cations. All of these compounds are explosive. The authors' interests are in developing "green explosives," such as explosives which do not contain toxic elements like lead (found in many primers) or perchlorate (used in rocket fuel.)

They prepared CN7 salts with both metal counter ions (Li, Na, K, Cs and Ca) and ammonium-type ions (NH4, N2H5, CH6N3 and CH7N4). The nitrogen salts were relatively stable, but the metal salts required a LOT of care given the description in the paper. The lithium and sodium salts were "relatively" stable - quotes in the original. Of the potassium salt, the paper says that even small amounts explode violently. They managed to isolate three crystals of the cesium salt and "a few hours later the whole preparation exploded spontaneously." These compounds are not to be taken lightly.

The next time a student asks if we can make something that explodes, I may just share with them the caution from this paper:
5-Azido-1H-tetrazole as well as its salts ... are extremely energetic compounds with increased sensitivities towards various stimuli. Therefore proper protective measures(safety glasses, face shield, leather coat, earthened equipment and shoes, Kevlar gloves and ear plugs) should be used at all time during work .... All compounds should be stored in explosive cases since they can explode spontaneously.
Once they safely obtained crystals of the salts, they determined their crystal structures. Hydrogen bonding seems to play a role in stabilizing these compounds. All of the nitrogen-cation salts were fairly stable, and their crystal structures show a fair amount of hydrogen bonding between the CN7 ions and the counter ions. The Li and Na salts crystallized with one water of hydration. The presence of water in these crystals seems to stabilize them through hydrogen bonds. The most reactive salts, K and Cs, have no waters of hydration and make no hydrogen bonds in the crystal. The other metal salt studied was Calcium. The Ca salt was also relatively stable, and co-crystallized with about 4.3 waters of hydration per Ca so there will be a lot of hydrogen bonding here as well.

The authors measured a number of properties of these compounds which had not been done previously. However, in the end they concluded that they are probably too sensitive for practical applications.

Thomas M. Klapötke, Jörg Stierstorfer (2009). The CN Anion Journal of the American Chemical Society, 131 (3), 1122-1134 DOI: 10.1021/ja8077522

Saturday, February 7, 2009

Scott McCloud on comics | Video on

A fascinating look at the world and story telling from the perspective of a comic book artist.

Thursday, February 5, 2009

Games to Exercise Your Brain

Check out these online games for exercising your brain:

In Assembler you have to move objects around to solve the puzzle.  There are boxes, boards and barrels and they all obey the laws of physics.  Each level is a little harder than the last.

FreeRice quizes you on vocabulary, adjusting to your skill level.  Might be good practice for preparing for the GRE.  There are other quizes too: Math, Foreign languages, Atomic Symbols, Geography and even paintings.

GeoSense tests your knowledge of geography.  You have to click on the location of a city within 10 seconds.  Your score depends on both speed and accuracy.  You can choose US cities, European cities or World cities.

Wednesday, February 4, 2009

HIV1 Protease and "Flap" Orientations

Enzymes are the machines of the cell - they make almost all of the chemical reactions that take place within a cell happen in a realistic time scale. They are able to do this because they bind specifically to a target molecule (the substrate) and convert it into a new molecule.

There are two models that are frequently used to describe how this "binding" works. The simplest is the Lock-and-Key model which assumes that the enzyme is a rigid molecule with a hole in it, rather like a lock and its keyhole. If a key has the right size and shape to fit into the keyhole, it might be able to open the lock. The enzyme has an opening called the active site - molecules with the right size and shape can fit into this active site and be modified by the enzyme. A drug (an inhibitor) can be designed that has the right size and shape to fit into the active site, but then it gets stuck. Once the active site is blocked by the inhibitor, the enzyme can no longer convert substrate molecules and it no longer works.

This model is rather limited - enzymes are often quite flexible. The second model, called induced fit, says that the enzyme changes shape when it binds to the substrate or inhibitor. If this happens, it will be important to know not only what the active site is like, but you also need to know how the enzyme changes when it binds to the substrate or inhibitor if you want  to design an effective drug.

Two recent papers examine how binding to an inhibitor may affect the shape of HIV-1 protease. HIV-1 protease (HIV PR) is an essential enzyme in the functioning of HIV and the target of many drugs for treating AIDS. If HIV-1 protease can be inhibited, none of the other proteins needed by HIV will get processed into their active forms.
HIV-1 protease bound to an inhibitor. Image from

Drug Pressure Selected Mutations in HIV-1 Protease Alter Flap Conformations looks at mutations in HIV-1 protease.  When HIV is exposed to protease inhibitor drug cocktails they observe mutations in HIV PR, especially in the two loops or flaps that cover the active site.  Mutations that reduce the ability of the drug to bind to the enzyme active site will be resistant to the influence of the drug.  Changes in the active site itself would obviously have an affect on the ability of the drug to bind effectively, but why would the protein develop mutations in the flap region, which is not directly related to the active site?  By looking at the orientation of the flaps when different inhibitors are bound to the mutants, they suggest that the flaps adjust to accomodate the binding of the substrate/inhibitor in order to fine tune the binding strength.

The second paper, Dynamics of “Flap” Structures in Three HIV-1 Protease/Inhibitor Complexes Probed by Total Chemical Synthesis and Pulse-EPR Spectroscopy, also looks at the flaps and inhibitor binding.  They also see evidence that the flaps move in response to the nature of the substrate as it is bound to the enzyme.  The reaction catalyzed by HIV PR involves two distinct chemical steps, so they chose inhibitors that resembled different stages along the reaction sequence:  during the first step, between steps one and two, and during step two.  They conclude that the flaps move to fine-tune the interaction between the enzyme and the substrate as the reaction procedes.

Both papers report evidence of "induced-fit" behavior in the way HIV PR interects with it's substrate.  Understanding what role the flaps play in substrate binding can lead to better drug s for treating Aids.

Luis Galiano, Fangyu Ding, Angelo M. Veloro, Mandy E. Blackburn, Carlos Simmerling, Gail E. Fanucci (2009). Drug Pressure Selected Mutations in HIV-1 Protease Alter Flap Conformations Journal of the American Chemical Society, 131 (2), 430-431 DOI: 10.1021/ja807531v

Vladimir Yu. Torbeev, H. Raghuraman, Kalyaneswar Mandal, Sanjib Senapati, Eduardo Perozo, Stephen B. H. Kent (2009). Dynamics of “Flap” Structures in Three HIV-1 Protease/Inhibitor Complexes Probed by Total Chemical Synthesis and Pulse-EPR Spectroscopy Journal of the American Chemical Society, 131 (3), 884-885 DOI: 10.1021/ja806526z

Monday, February 2, 2009

Periodic Table Duvet Cover - Neatorama

Normally I don't care for household items that have a periodic table on them, but this is pretty cool.

Neatorama has a post on this homemade duvet cover with a periodic table on it. You can even see how it was made at
Periodic Table Duvet Cover - Neatorama