Book of Abstracts: Albany 2005
A Survey of the Protein Folding Problem
An evolution of the protein folding problem, from experiment to theory, will be discussed. Initially, attempts were made to determine protein structure by use of physical chemistry (before the introduction of x-ray and NMR techniques). After the Anfinsen experiment was reported, attention was turned not only to determine the structure but also to determine folding pathways using bovine pancreatic ribonuclease A as a model. Experimental studies of the folding pathways of this protein both with and without intact disulfide bonds (disulfide-intact and oxidative folding, respectively) were carried out, and will be discussed.
The aforementioned physical chemistry studies yielded distance constraints which led to our development of theoretical computational methods to compute protein structure. More recently, the theoretical methods have been extended to compute folding pathways. These two theoretical aspects of the protein folding problem, i.e., computation of both structure and pathways, will be discussed.
Harold A. Scheraga
Baker Laboratory of Chemistry and Chemical Biology