Principal Investigator Jonathan King
Co-investigators Bonnie Berger , David Gossard
Professor Bonnie Berger in Applied Mathematics together with Professor Lenore Cowan (Tufts), Matt Menke, and Phil Bradley (now at UW Seattle) have led a collaborative effort to develop algorithms that can identify sequences which will fold into parallel ß-coils. The program, Betawrap, successfully finds the known beta-helices in the Protein Data Bank with no false negatives or positives. When run on genebank sequences, it scores very highly a few hundred sequences almost all of which are from microbial species, including numerous human pathogens. This may reflect the special function of parallel ß coils in binding long floppy polysaccharides important in host cell recognition.
In collaboration with Judith Klein-Seetharaman and Deborah Weisser at Carnegie-Mellon and University of Pittsburgh Medical Center, Dr. Peter Weigele and Welkin Pope are using biological language modeling tools to examine the sequence control of ß-helix and triple ß-helix formation.
In collaboration with Professor David Gossard in Mechanical Engineering, we are developing kinematic models for subunit polymerization into icosahedral shells, as well as the lattice transformations required for the procapsid to capsid transition in dsDNA viruses. These lattice transformations provide a model for a very general set of protein subunit conformational changes that occur not in solution but in constrained polymeric structures.