Protein Portraits






         The aesthetic alchemy of life

Week 2

Artworks representing ATP synthase

Let’s examine a really successful use of molecular graphics for understanding protein structure and function. Chapter 2 of The Machinery of Life gets the ball rolling (gets the turbine turning?) with a splendid graphic illustration of ATP synthase, the enzyme that manufactures ATPThe 3D structure of the enzyme molecule is represented as a static multimeric protein embedded in a membrane (not shown in the book but shown below in Goodsell’s illustration in The Molecule of the Month for Dec. 2005):

ATPsynthase

Other graphic artists have added animation to illustrate how protons streaming from one side of the membrane to another provide kinetic energy that forces the inner axle of the ATP synthase to turn relative to the stationary stator.  Here are some examples:

atpsynanim

Uc4UyfT

The dance of protein synthesis

Chapter 2 of The Machinery of Life then picks up on the theme of complementarity of nucleic acids as the basis for storing and transmitting genetic information.  This topic is especially relevant in our course, Protein Portraits, because nucleic acids serve as the blueprints and the catalytic machinery for building protein molecules.

Take a close look at Figure 2.6 and relish the finely crafted artistic view of the small subunit of a ribosome sitting in wait for the several other factors and ingredients required to build a new protein chain.  One of those items is the large ribosomal subunit (which you can view in its full glory as the October 2000 Molecule of the Month), while the others include the messenger RNA, a full palette of transfer RNA’s each charged with one of the twenty amino acids, a collection of initiation factors, and last but not least, empowering molecules of ATP and GTP.  While you can find dozens of staid but true representations of the process of protein synthesis in various biochemistry and cell biology textbooks, you might want to also spend 10 minutes to take a look at the animated dance version of protein synthesis found here as a youtube video (the dance is introduced by Paul Berg, the discoverer of DNA ligase).

protein_synthesis

The dancers and musicians are Stanford hippies from 1971.  But is this art?  Here’s a comment on the video made by the National Performing Arts Convention:

What ends up being an entertaining 70’s hippy dance fest (it really heats up around minute 9 when the groovy drums and flute come in) is also an interesting case study of using dance and movement as a way to visualize very complex and impossible to see biological processes.  Keep in mind that this is before the advent of complex computer modeling.

A similar though bleaker view of the dance video is presented here by the Turkish artis Elmas Deniz in the Istanbul-based forum called Open Systems:

Today my boyfriend showed me a video — which he found out about from an interview with Julian Assange and Google CEO Eric Schmidt [1] — directed in 1971 by Robert Alan Weiss for the Department of Chemistry of Stanford University. An epic about protein synthesis, where you can see a hundred hippie students making music, dancing in order to represent a biological event. Assange’s argument is that realizing the same type of performance as an education method would not be possible today …

No doubt there will always be a give-and-take between artistic creativity on one hand and science-technology on the other.  Working on our protein portraits gives us an opportunity to jump right in to the middle of that dance partnership.

Process artwork:  Depicting the dynamics of life

In Figure 3.2, Goodsell presents a highly original dynamic view of the process of cholesterol synthesis (well, he actually takes us only through to the lanosterol step, explaining that the completion of the cholesterol molecule requires additional steps).  Ordinarily we would see the process depicted in a much less graphic manner, as in the following chart taken off of wikipedia:

HMG-CoA_reductase_pathway

Both manners of depicting a dynamic process are successful, but which sticks better in your mind after closing the page?

Are there other ways of depicting the dynamics of cholesterol metabolism in the human body?  Of course!

Cholesterol art

Zeroing in on a protein structure in the PDB

Let’s look up one of the enzyme molecules shown in Figure 3.2, HMG CoA reductase.  Everyone is interested in this enzyme these days because it is the enzyme that is inhibited by the statin drugs, the drugs that block cholesterol synthesis.  One of the most informative examples of the structure of HMG CoA reductase is listed under the code name 1hwk in the PDB.  How did I discover this enzyme molecule in the PDB?  I used the dynamic duo of online resources that every protein artist will use often:

  • Good ol’ Wikipedia (I looked up the term “statin drug” and discovered an image of HMG CoA reductase which referred to the codename 1hwk), and then I used the amazing …
  • Protein Data Bank (I searched for “1hwk”, or I could haves searched directly for “HMG CoA reductase”).

1HWK_bio_r_250

 

Protein domains

Domains are compact arrangements of folded chains.  From a purely artistic perspective, you can think of a domain as a major substructure (a chunk) of the overall protein.  A domain stands apart from the rest of the structure. If a protein were a human body, the head would be one of its domains, the trunk another, the left arm another, etc.  Some proteins have a single domain, others have many.  A chain sometimes folds into a single domain , sometimes into multiple domains.  Myoglobin is a single chain and a single domain.  An IgG molecule includes four chains folded into six domains.

One of the great discoveries of the past decade is the conservation of domains across all of biology.  The biological world includes a few hundred domains as the canonical elements that account for the structures and functions of essentially all of the many thousands of existing proteins.  Long ago nature evidently discovered a set of compact machines (domains) and has used them creatively in assorted mix-and-match combinations.  This is amazing:  The many thousands of known protein structures (they all can be looked up in the PDB!) fold into just a few hundred generic protein domains.

  • For the artist, one very helpful exercise is to make 2-D sketches of 3-D proteins.  A 2-D “topological diagram” can serve as a quick and easy surrogate for a rotatable 3D computer model when you are trying to make sense of how a chain travels through a molecule.  Below are examples from Jane Richardson.  She is deservedly credited as the inventor of 2-D topological sketches of proteins. Note how her topo diagrams readily highlight the differences between superficially  similar alpha-beta class proteins:

  • An artist can take advantage of 2-D topologies while attempting to depict the complicated multi-domain and  oligomeric-structure of big protein molecules.  No matter which depiction the artist has in mind, it is useful to make some 2D top0 sketches:  Will you depict a small protein by showing its details, or will you smudge out the detail and portray a big protein?  The sketch book is your friend!
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