The long-term goal of this work is to contribute to a fundamental understanding of the 3-dimensional structures of proteins and the folding proteins and the folding process by which those structures are achieved.
The specific aims i nclude solving new protein structures; finding patterns and generalizations in the data base of known structures; and the de novo design, synthesis, and study of small model proteins. Currently active crystallography projects are acyl carrier protein; alcohol oxidase, a cell-binding domain of fibronectin, Cu,Zn superoxide dismutase for its water structure and the reduced form, and crystallization trials of the designed proteins. The primary tool for analysis and comparison of protein structures will be interactive computer graphics, including the development of new ways of representing and manipulating protein structures. De novo design of new model proteins will attempt to integrate all that is known about the target structure type, including quantitative calculations where feasible. Some of the designed proteins will be made be peptide synthesis and some by nucleic acid synthesis, cloning and expression. After purification, initial characterization will be done mainly by circular dichroism, laser Raman, calorimetry, and nuclear magnetic resonance (NMR). For both betabellin, a beta-sandwich protein made by peptide synthesis, and felix, a 4-helix cluster made by genetic methods, pure soluble protein has been produced which shows the correct structure type by spectroscopic methods. The necessary proof of structure must be done either by 2-D or by x-ray crystallography. Then these model structures can be used to test our own and other people's hypotheses about protein structure and folding, which should lead to improve control of biological, clinical, and industrial processes that depend on the folding of particular proteins. Eventually, the designed proteins should be capable of serving as controllable templates on to which desired new binding and catalytic functions will be built.
| Richardson, Jane S; Richardson, David C (2014) Biophysical highlights from 54 years of macromolecular crystallography. Biophys J 106:510-25 |
| Richardson, Jane S; Richardson, David C (2013) Studying and polishing the PDB's macromolecules. Biopolymers 99:170-82 |
| Richardson, Jane S; Richardson, David C (2013) Doing molecular biophysics: finding, naming, and picturing signal within complexity. Annu Rev Biophys 42:1-28 |
| Wales, Thomas E; Richardson, Jane S; Fitzgerald, Michael C (2004) Facile chemical synthesis and equilibrium unfolding properties of CopG. Protein Sci 13:1918-26 |
