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FREDERIC M. RICHARDS

Professor Richards passed away on January 11th, 2009. 

Protein folding and structure
Both experimental and theoretical approaches are used in attempts to identify and quantitate the major forces that control protein folding pathways and that are responsible for specifying the unique biologically active, native structures. A major emphasis at this time is on geometrical packing in the protein interior and on examination of the protein-solvent interface. These studies involve preparation of single and multiple site mutants by both molecular biological and synthetic chemical techniques. The structures by crystallography or NMR, and the thermodynamic properties by colorimetry, of these mutants ore then determined. The experimental approaches are supplemented by theoretical studies of packing geometry and the development of the necessary computer algorithms for this purpose.

We are attempting to develop a procedure for the experimental determination "accessible surface area". At present, this parameter can only be calculated from molecular models. Knowledge of this area should be useful in studying protein folding intermediates and other ensembles representing a collection of related conformations rather than a unique structure. Changes in this area during association - dissociation reactions that occur in systems not amendable to X-ray or NMR structure studies could be elucidated by such a technique and used to assist in model building and in analysis of the energetics of these reactions.

Publications
Richards, F.M. and Lim, W.A. (1994). An analysis of packing in the protein folding problems. Quart. Rev. Biophys. 26:423-498.

Hellinga, H.W. and Richards, F.M. (1994). Optimal sequence selection in protein of known structure by simulated evolution. Proc. Natl. Acad. Sci. USA, 91:5803-5807 .

Lim, W.A., Richards, F.M. and Fox, R.O. (1994). The Structural Determinants of Peptide Binding Orientation and Sequence Specificity by SH3 Domain. Nature 372: 375-379 .

Last updated 02-10-2009