Proteins are the nano-sized machines that perform virtually all of the functions constituting the molecular basis of life. They serve as cleaners, builders, motors, messengers, and transporters in our cells. Each protein is a chain composed of twenty types of "beads" called amino acids. Each protein has a unique sequence of amino acids, which is encoded by a segment of DNA responsible for making this protein (called a gene), and it is this sequence that ultimately determines the function of the protein. After it is manufactured, a protein chain will fold into a unique three dimensional conformation, called the native fold, which determines the function of the protein. To me the most beautiful aspect of this process is that a protein can find its very complicated native fold by itself, purely based on the sequence of amino acids constituting the protein. Indeed, there are so many ways a protein chain can potentially fold itself up that it would take more than the age of the universe to try them all, even at the speed limit of molecular motion. Given that life is evidently possible, the question is: how does a protein find its native needle in an astronomically-sized haystack of possible conformations? To resolve this conundrum, called the Levinthal paradox, my thesis showed that, because many types of amino acids like to congregate in the center of proteins to avoid water (hydrophobic clustering), the resulting number of ways that a protein can fold itself and still preserve the hydrophobic clustering is so small that most protein domains can find their native fold by trial-and-error within seconds. Thus, in a quantifiable yet unexpected way, water is responsible for the feasibility of life.
The emergent behavior of protein folding, in which the dynamics of the chain takes on a life of its own and becomes more than the sum of its parts, is very powerfully illustrated by the language of dance. The frustration of making and breaking numerous bonds, trying many different conformations, and yet never finding the native fold (the first dance) contrasts with the fluid motion of the second dance which culminated in the "aha" moment when all of the amino acids click into place. It was satisfying and a bit surreal to see the physics of the problem playing out spontaneously within the dance. For example, just as for real proteins, the dancers (including I) had trouble finding the native fold in rehearsal without the hydrophobic amino acids clustering together. In a similar vein, when we found the native fold, the network of bonds (represented by handshakes) united our movement into a single resonant frequency. These are two examples of emergent behavior that seemed to apply not only to proteins, but to the dancers playing the part of the protein.
I was very fortunate to benefit from the deep well of talent and experience of my collaborators in this project. My choreographer and partner, Elaine, crafted specific dance vignettes that elevated the piece from pantomime to dance, and our camerawoman and editor, Alexi, brought out the best in our movement and synced it to the music. The dancers, which included high school dance students as well as dance teachers (and a lone scientist), all gave it 100% and made the dance their own, contributing numerous movement suggestions that gave extra nuance to the piece. The most satisfying part of the process was to see everyone learn something new and unexpected, whether about science, dance, or the possibility of connecting between generations, cultures, and disciplines.
The scientific results presented here received the 2012 Clauser Prize for best Caltech PhD thesis and are reported in:
1) M.M. Lin and A.H. Zewail, "Hydrophobic forces and the length limit of foldable protein domains," Proc. Natl. Acad. Sci. 109, 9851-9856 (2012)
2) M. M. Lin, and A. H. Zewail, "Einstein Lecture: Protein Folding – Simplicity in Complexity," Ann. Phys. (Berlin) 524: 379-391, 2012 (cover).