MOLECULAR MODELLING SYSTEM

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Funds are requested to purchase a Molecular Modelling System (an Evans and Sutherland PS 300) and the computer hardware upgrade necessary to support it. This proposal arises from a critical need by a number of professors at BU for "three-dimensional" model building of proteins and the development of hardware and software to provide that . This group is particularly interested in the structure of membrane proteins, a burdgeoning area in which little direct information is known. Regular access to such a facility is not currently available to these faculty at Boston University (BU). The PI has had extensive experience with instruments similar to the one requested and would provide training for the other users. BU is building a Center for Science and Engineering, and the instrument would be located in new space in the relocated Chemistry Department, adjacent to the PI's research lab and office, which is scheduled for completion in the fall of 1984. Many of the projects which would use this Molecular Modelling System involve the exploration of a particular structural feature of membrane proteins: their amphipathic character, i.e. polar on one side and non-polar on the other side. This nature has been demonstrated crystallographically for the protein crambin, which can associate with lipids, and suggested for other proteins under study for this proposal. The major projects are: development of an automated method of three-dimensional structure prediction for homologous proteins, application of these methods to plasminogen and its kringles (proteins in the blood clotting system), and model building for myelin proteolipid in the lipid membrane, for bacteriorhodopsin and its chromophore in a bilayer, for apo-A-I protein from high density lipoprotein, for mannitol permease transmembrane and catalytic domains, and for phycobiliproteins and the phycocyanobilin chromophore. Skills of the investigators complementary to model building, such knowlege of protein crystal structures; Circular Dichroism, FTIR and Raman spectroscropy correlated with empirical methods of secondary structure prediction; sequencing and chemical modification; and small angle scattering, will be applied to these predictions.