First Principles Modeling of Protein Folding and Secretion in Saccharomyces cerevisiae
 

Kenneth J. Kauffman, Anne S. Robinson, Prasad S. Dhurjati, Francis J. Doyle III
University of Delaware
Department of Chemical Engineering
Newark, DE 19716
kkauffma@udel.edu
(302) 831-6851
 

Eukaryotic protein folding occurs by a series of complex reactions. Insight into these reactions can provide an improved understanding of the limitations to protein folding in the cell and methods to overcome these limitations. Previously, there have been few attempts to model all of these steps simultaneously to obtain an improved understanding of the bottlenecks in protein folding. We have developed a first principles based, nonlinear model based on the known biological reactions and regulatory pathways. In portions of the model, key reactions have not yet been completely identified. In these cases, mathematical approximations for observed experimental phenomena have been used. The resulting model provides insight into potential avenues for experimental improvement of the yeast secretory pathway, improved understanding of the biological implications of the pathways, indications of potential control mechanisms, and direction of future sensor development. We will discuss several preliminary findings from the model and the experiments suggested from the model outcomes.