RESEARCH INTERESTS:
High Throughput Biophysics One of the major unanswered questions in biology has to do with how to predict the three-dimensional structure of a protein from its amino acid sequence. For many years investigators have generated and characterized tens of mutant proteins at a time to test hypotheses concerning the determinants of protein structure. We have extended this approach using high throughput techniques (robotics, combinatorial libraries and semi-automated instrumentation) to characterize hundreds or even thousands of mutants at a time to test hypotheses. These large numbers allow us to utilize a more formal version of the mathematics of hypothesis testing. This extension should allow us to assess the contributions made by any postulated interaction, even in complex circumstances where there are likely to be other unknown stabilizing effects; a process that is hard to accomplish with only a few tens of mutants. This approach, for the first time, lets us determine whether or not the model tested is 'complete'. For example, our analysis of 455 variants of eglin c (our favorite model protein) drawn from a library mutated at four alpha-helical solvent exposed sites indicates that the effects previously identified by the biophysics community explain ~92% of the behavior of 90% of the mutants. This also means that new effects will need to be identified to explain the behavior of the remainder of the mutants.
RECENT PUBLICATIONS:
Knaggs MH, Salsbury FR Jr, Edgell MH, Fetrow JS. Insights into correlated motions and long-range interactions in CheY derived from molecular dynamics simulations. Biophys J. 2007 Mar 15;92(6):2062-79. Epub 2006 Clarkson MW, Gilmore SA, Edgell MH, Lee AL. Dynamic coupling and allosteric behavior in a nonallosteric protein. Biochemistry. 2006 Jun 27;45(25):7693-9 Fetrow JS, Knutson ST, Edgell MH. Mutations in alpha-helical solvent-exposed sites of eglin c have long-range effects: evidence from molecular dynamics simulations. Proteins. 2006 May 1;63(2):356-72 | 
Biochemistry and Biophysics - UNC School of Medicine
