A Theoretical Method for the Determination of Helix Configuration in Membrane Proteins

Makiko SUWA (suwa@tuat.ac.jp)
Takatsugu HIROKAWA
Shigeki MITAKU (mitaku@tuat.ac.jp)

Tokyo University of Agriculture and Technology, Faculty of Technology,
Nakamachi, Koganei, Tokyo 184, JAPAN


A theoretical method for structure prediction of membrane proteins was developed based upon physicochemical calculations, comprised of three steps. In the first step, the polar interaction field of a transmembrane helix was characterized by a probe helix method in which interaction energy between a transmembrane helix and a probe helix was calculated. A jigsaw puzzle problem in the second step was solved by using a binding maps of pairs of helices. Binding energy obtained from the polar interaction field was plotted in a binding map as functions of the orientation angles of the two helices. Finally, helix configuration determined by the analysis of binding maps was refined, minimizing the binding function of the whole system.

In order to deal with a jigsaw puzzle problem, several principles of the folding of membrane proteins have been assumed: (1) The molecular structure is formed according to some folding pathway. (2) The dominant interaction in hydrophobic region of membrane is the polar interaction. (3) Transmembrane helix can be regarded as a stable rod with charge distribution on it. The comparison of the predicted structure of bacteriorhodopsin with the experimental one revealed that the reconstruction of the relative position and the orientation of transmembrane helices is possible by this method. Applying this method to rhodopsin, the configuration of transmembrane helices was determined, which was quite similar to the experimental configuration of transmembrane helices. The mechanism of the structural change of rhodopsin by cis-trans isomerization of retinal was suggested from the predicted structure.