Protein dynamics and function
Last updated 21 February 2007
Although I havenÕt looked at these problems much in the past ten years, for quite some time my collaborators and I were interested in the dynamics of biological molecules and the way in which these dynamics connect to their functions. One particular obsession was with the interplay between classical and quantum dynamics in these large molecules.
Papers are in chronological order, most recent papers at the top. Numbers refer to a full list of publications.
[38.] A new look at the primary charge separation in bacterial photosynthesis. SS Skourtis, AJR DaSilva, W Bialek & JN Onuchic, J Phys Chem 96, 8034-8041 (1992).
Photosynthesis begins with a photon induced transfer of an electron from one large molecule to another, both held in a protein framework. This step is complete in ~ 3 psec, one of the fastest reactions of its type ever observed. Chemistry as we usually think about it operates in the limit where reactions are slow compared with internal molecular relaxation rates, and on these grounds alone it seemed unlikely that the initial event of photosynthesis could be thought of as a conventional chemical kinetic process. In more detail, if one tries to estimate the matrix elements among the relevant electronic states and use the golden rule to calculate the transfer rate, there are considerable uncertainties but it seemed hard to get the right answer. In this work we showed that there is a surprisingly broad regime in which electronic matrix elements, vibrational level spacings and relaxation rates are all comparable, so that one can be poised in between the golden rule regime and coherent oscillation. Since irreversibility is possible only after the destruction of quantum coherence, this regime is one in which the reactions are as fast as possible, and we argued that predictions of the theory in this regime are consistent with various aspects of the phenomenology in photosynthesis. As we were completing the paper, a new set of ultrafast spectroscopy experiments at lower temperatures revealed the coherent oscillations that would occur in our scenario if relaxation rates were reduced.
[37.] Vibrationally enhanced tunneling as a mechanism for enzymatic hydrogen transfer. WJ Bruno & W Bialek, Biophys J 63, 689-699 (1992).
The transfer of hydrogen atoms or ions is central to a wide variety of biological processes. There has long been interest in the possibility that these reaction proceed by quantum tunneling, but the evidence was murky at best. In many enzymes the hydrogen transfer reactions show anomalous isotope effects, as expected for tunneling, but also substantial temperature dependencies, as expected for thermal activation. In this work we considered a scenario in which (classical) protein motions could enhance the quantum tunneling of hydrogen in enzymatic reactions by causing fluctuations in the shape of the barrier. In the semiŠclassical limit we showed that almost any reasonable model in this class leads to a very simple phenomenology that fits the puzzling pattern of temperature dependent kinetic isotope effects. New experiments have provided yet stronger evidence for the importance of protein enhanced tunneling, and current theoretical activity is concentrated on detailed quantum chemical calculations that embody the basic scenario proposed in our work. I found it very pleasing to see how biology could exploit this interplay between classical and quantum dynamics.
[35.] Bleaching of the bacteriochlorophyll monomer: Can absorption kinetics distinguish virtual from two-step transfer? JS Joseph, WJ Bruno & W Bialek, J Phys Chem 95, 6242-6247 (1991).
[20.] Protein dynamics and reaction rates: ModeŠspecific chemistry in large molecules? W Bialek & JN Onuchic, Proc Nat Acad Sci (USA) 85, 5908-5912 (1988).
[16.] Simple models for the dynamics of biomolecules: How far can we go? W Bialek, RF Goldstein & S Kivelson, in Structure, Dynamics and Function of Biomolecules: The First EBSA Workshop, A Ehrenberg, R Rigler, A Grslund & LJ Nilsson, eds, pp 65-69 (Springer-Verlag, Berlin, 1987).
Here we studied a simple model for the initial events in the visual pigments, combining intuition from condensed matter physics work on conjugated polymers with a (then) novel simulation technique that combined molecular dynamics with diagonalization of a model Hamiltonian for the electrons. Much as in our discussion of the primary event in photosynthesis , the essential steps occur on a time scale such that quantum mechanical coherence is preserved. Subsequent experiments detected the coherence effects expected from the theory, although it would be an overstatement to say that the theory was confirmed. These rapid photoinduced events are some of the only cases I know where quantum coherence really is important in a biological process.
In retrospect the simulation method used here is a sort of poor man's CarŠParinello method (and done at the same time), using tight binding rather than density functionals. I think it is quite a powerful technique, and we should have made more of it at the time.
[15.] Protein dynamics, tunneling, and all that. W Bialek & RF Goldstein, Phys Scr 34, 273-282 (1986).
[1.] Contraction of glycerinated muscle fibers as a function of the ATP concentration. R Cooke & W Bialek, Biophys J 28, 241-258 (1979).