The hypothesis that transmembrane helices are independently stable folding units will be examined by studies of fragments of bacteriorhodopsin (bR) and intact bR reconstituted in lipid vesicles. The consequences of sequence modifications will be studied in a collaborative project with Dr. Khorana at MIT. The interaction of fragments with each other will be followed using vesicle fusion techniques, neutron and X-ray diffraction structural methods, spectroscopic measurements and chemical modification techniques. The protein folding problem represents one of the most important scientific challenges facing biochemists, biophysicists and physical chemists as well as the major gap in the understanding of the flow of information in living systems. Understanding the three-dimensional implications of the linear, abstract information in DNA can be regarded as a true understanding of the genetic code. Important principles remain to be established and any attempt to engineer proteins de novo or to understand medical problems in terms of altered genetic information must benefit enormously from insights concerning macromolecular folding. However, in spite of the practical importance and intellectual fascination of the problem, structural prediction and the determination of pathways of folding remain elusive goals.
