Alan M. Friedman
Associate Professor of Biological Sciences
Extending our earlier and continuing efforts to determine new protein structures, we are applying tools that we are developing ourselves to answer several of the oldest questions about protein structure. How does the amino acid sequence determine structure and function? How does all the rest of the protein affect the function of the active site? Our new tools combine computation and experiment to gain insight into these questions that neither alone can provide. Computation ("bioinformatics") is used to select the most informative experiments by analyzing the natural experiments of existing protein sequences, while experiment is used to restrain and refine the computation. Experimentation typically involves making and analyzing large numbers of proteins that recombine existing sequences (chimeric proteins) and solution phase assessments of protein structure and dynamics.
Our crystal structure of the BsoBI restriction enzyme (protein backbone in blue and yellow) complexed with DNA (backbone in green). Mutants affecting the specificity of restriction enzyme cleavage (shown as colored spheres) are located throughout the structure, including distant from the site of cleavage (shown as the two black spheres).