Monday, October 3, 2011
Some years ago, I made a dance that celebrated the molecular choreography of three transducing NTPases. These are molecules, also known technically as "motors", that make things happen in the cell. They all use a fuel called adenosine triphosphate (ATP). Having misplaced the relevant files several times, I decided to post it here, with these notes.
Thoughts about the NTP Celebration Suite – Cincinnati July 2002
Discussing myself over the years with colleagues and friends, I’ve describe myself as an eclectic, pragmatic, Platonist – I have worked in a wide variety of areas, from biological electron transport to the origin of life, mechanistic enzymology, statistics in experimental design and screening (phase diagram analysis), the crystallographic phase problem, bioinformatics, and allostery. Each time I’ve changed into a different area, I’ve had to re-define myself, learning new things. It’s been a pretty good run, all things considered. Although I’ve embraced many different techniques for pragmatic reasons, however, I feel inwardly committed to one ideal form or another, and consequently am fascinated with models. I question data first, when they conflict with models I’ve invested in. For that, I consider myself a Platonist as opposed to an Aristotelian.
I read in Aaron Klug’s biography from the Nobel pages that his wife is a modern dance enthusiast. I hope it does no injustice to Aaron to reflect on his role in shaping these aspects of my professional life. I was in Cambridge barely long enough to learn where the lifts and centrifuges were. Yet, Aaron and Roger Kornberg both proved to be major intellectual role models, to whom I return in my mind surprisingly frequently for spiritual renovation. So, I am deeply grateful that Aaron was generous enough to share his lab with me for that brief, but very formative year.
Interpreting Molecular Choreography
The dance, NTP Celebration Suite, is an interpretive piece drawing inspiration from the three-state behavior of molecular motors. I want to share some of the history of this dance. I learned late in life that I derive a deep joy from dance. When I was in secondary school (grade 7-8) I enjoyed ballroom dancing (in those days, I tolerated it better than my friends!). At one point, I had the opportunity to perform in a recital as the partner of one of the instructor’s serious dance students. It was truly a lovely experience, and I seemed to have done pretty well, because the instructor came to me afterward and told me I should consider studying dance.
The Research Triangle has a major cultural resource in the American Dance Festival, ADF, located on the Duke Campus in Durham each spring and summer drawing the best modern dance companies from around the US and the world. I re-discovered dance in the mid 1990s, after we saw Pilobolus, a marvelous company with musical grace, gravity-defying choreography, a sense of humor, and a very full sense of what the human body can and cannot do! We have had season’s tickets ever since. Some years later, I decided to volunteer at ADF, and have been a docent for their summer school tours ever since. The classes are every bit as exciting for me as the professional performances.
Being ACA Past President
So it was natural that I thought of dance on my first terror-stricken moments after I was elected President of the American Crystallographic Association and thus would have to present a Past President’s address at an annual banquet three years later. The ACA Past President’s address is a wonderful tradition, and the previous ones I had witnessed had a very intimidating variety of creativity and intelligence! I began to talk about what I might do with Bill Duax (Past President of the IUCr), whose wife and daughter are both dancers. I told others, thinking that if I told enough people, I would HAVE to do make good on my plan.
In Memoriam Pierre Morell
An especially poignant moment came at our departmental Christmas party six months before the banquet when I would have to perform. I was talking about the idea to friends, and one of them, a neurochemist named Pierre Morell, got excited and volunteered to invest in the project and help me hire a choreographer! Sadly this colleague very soon fell ill with a brain tumor and died within four months. So the dance will always have that personal memory.
The suite of three dances (myosin, kinesin, and F1 ATPase) did not spring fully blown. I actually had worked out much earlier a crude version of the ATPase segment after a Gordon Conference at which Andrew Leslie presented the F1 crystal structure. That structure was a tremendous stroke of luck for Andrew: three successive states analogous to those it had taken me a decade to solve for tryptophanyl-tRNA synthetase – Open, Pre-transition state, and Products – were present in the same crystal structure, owing to the cyclic symmetry of the ATPase. Three in one go! I was quite envious of people like Andrew and Ivan Rayment, because I recognized the enchantment of free-energy transduction, but had not had (or made) the same opportunities they had had. Yet, the F1 ATPase was indeed a wondrous and very beautiful structure, both intellectually and esthetically. By celebrating it with a dance, I found a way to “own” it in my own way, without taking anything from those who had solved the structure and my envy dissipated.
Anyhow, chance brought Joy Javits into my path. The daughter of a wonderful Republican Senator from New York, Jacob Javits, and recognizably his kin, Joy is a choreographer who enjoys working with eccentric academics. She had worked before with a maths professor I knew pretty well, and was a perfect match for this project. We worked out something of a contract, and went to work, with roughly eight weeks to go. I described the ATPase structure and what it meant functionally to her and showed her a schematic video of the ATPase as well as Ron Milligan’s molecular videos of kinesin and myosin, and she started to work with me. Joy has a wonderful imagination, and she quickly seized what it was I wanted to capture about the three-state behavior of transducing NTPases. I got really excited when I selected the music and found that I could synch it with the videos. We decided that it would be a multi-media performance.
When Joy found I had selected a Doc Watson rag for the ATPase segment, she immediately suggested a clog. Clogging is a dynamic folk dancing technique native to North Carolina. I had tried and failed several times previously to learn to clog. Joy took me in hand and carefully worked through the various steps, and soon I found myself doing it! She also suggested a simple two-step to go with the Myles Davis Blues accompaniment to the kinesin segment. The lament from Talk to Her by Alberto Iglesias for the myosin segment was the first one I selected. It matches Ron Milligan’s video just right, and was perhaps my favorite choice in the end. I had great fun editing the soundtrack and video to synchronize them. Little by little things fell into place.
Chicago Art Institute: Dress Rehearsal
I went to Chicago a couple of days before the ACA meeting in Cincinnati to give a lecture to the ACA summer course, and stopped in to visit with my daughter, Emily, then at the Chicago Institute of the Arts. Emily had a recital for an improvisation course that day, and I was privileged to watch it. Afterward, over snacks, I got to talking with the instructors and students, and it came out that I was working on the dance. We also spontaneously realized that I had yet to perform the entire suite in one go. So I got out my laptop and had the chance to do dress rehearsals for two different audiences in a small room where the sound quality from the laptop was pretty good. Their enthusiasm was an incredible tonic!
In the end, the performance went over very well. It was accompanied by a short, non-science reminiscence, not included in the video. There was a photographer but no video camera (I had kept the whole thing so secret that this was impossible to arrange without spilling beans). It was glorious fun for me, and I think others enjoyed it.
A common theme in all three parts of the suite is that my arms represent the three successive states – ligand-free, ATP, ADP plus Pi – encountered during a single cycle of ATP hydrolysis (or synthesis in the case of the F1 ATPase. There is an introductory phase showing these three states for the kinesin and F1 segments, whereas the myosin segment begins with the ligand free (attached, rigor) state and proceeds without explanation. There is no footwork to speak of in the myosin segment, whereas there are steps associated with the other two.
The video was shot by Alex Tropsha, a colleague in Bioinformatics here at UNC, at a reprise I did for the Triangle Biophysics Symposium in 2004. It is not professional, but then, neither am I!