Effect of single point mutations on the aggregation propensity of a model protein

BIOT 196

Dusan Bratko, Department of Chemistry, Virginia Commonwealth University, and Department of Chemical Engineering, University of California, 1001 W Main St, Richmond, VA 23284-2006, Troy Cellmer, cellmert@niddk.nih.gov, Laboratory of Chemical Physics, NIDDK,/NIH, 9000 Rockville Pike, Bethesda, MD 20892-0520, John M. Prausnitz, Department of Chemical Engineering, University of California, and Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, and Harvey W. Blanch, Department of Chemical Engineering, University of California at Berkeley, Gilman Hall 201, Berkeley, CA 94720-1462.
Sequence engineering represents a promising route toward control of protein aggregation. Using parallel tempering simulations, we carry out a thermodynamic analysis of mutation effects on the aggregation proclivity of model proteins. The different criteria for the selection of point mutations we discuss are based on the mutation impact on the stability of the protein native state, the aggregate stability, and contact maps comparing participations of specified residues in intra- and interprotein bonds. Through the comparison of folding/aggregation free-energy landscapes of the wild type protein and its variants, we demonstrate the possibility of using guided mutations to modulate protein aggregation propensity without affecting the native state structure and concomitant function of the protein.
 

Biophysical and Biomolecular Symposium: Protein-Protein Interactions
8:00 AM-11:00 AM, Wednesday, 13 September 2006 Hilton San Francisco -- Imperial B Ballroom, Oral

Division of Biochemical Technology

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006