I investigate the structure of protein energy landscapes, symmetries of three-dimensional structures as key factors governing the shape of protein morphospace. Proteins, like organisms, exhibit a non-uniform distribution of present forms. Proteins can be divided into different sized groups of individual forms according to their fold (topology), characterized by secondary structure elements (a helix and b sheet) and their arrangement. Despite the fact that only a small percentage of existing protein structures has been solved experimentally and the representation of form in structural databases is highly biased, it has been repeatedly shown that the distribution of individual protein structures between folds is far from uniform (Chothia, 1986, Richardson, 1981, Ptitsyn, and Finkelstein, 1980). Out of the 564 folds represented in SCOP (structural protein classification) ten folds account for one third of the structures in PDB (Protein Data Bank) (Brenner, et al., 1997, Orengo, et al., 1994, Zhang and DeLisi?, 2001). These folds, also known as superfolds(Orengo, et al., 1994, Salem, et al., 1999), include globin, updown, trefoil, Tim barrel, OB roll, doubly wound, immunoglobulin, UB roll, jelly roll, plaitfold (Fig.1and Fig. 2) (Salem, 1999). One possible factor generating the non-uniform distribution of proteins among folds is the physico-chemical properties that determine topological constraints shaping the realized morphospace of proteins (Anfinsen, 1973; Levitt et al., 1997). Therefore, proteins provide us with a good model for studying patterns in phenotype space and processes underlying the generation of morphotypes.

Some references:

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Babajide, A., Farber, R., Hofacker, I., Inman, J., Lapedes, A.S., and Stadler, P. (1997). Neutral networks in protein space: a computational study based on the knowledge-based potentials of mean force. Fold. & Des. 2, 261-269.

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Chothia, C. (1992) One thousand families for the molecular biologist. Nature. 357, 543-544.

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Jones, D.T. (1998) Do transmembrane protein superfold exist? FEBS Lett. 423, 281-285.

Holm, L. and Sander, C. (1998). Dictionary of recurrent domains in protein structures. Proteins: Struct. Funct. Genet. 33, 88-96.

Huynen, M.A., Stadler, P.F., and Fontana, W. (1996) Smoothness within ruggedness: the role of neutrality in adaptation. Proc. Natl. Acad. Sci. USA 93, 397-401.

Govindarajan, S., Recabarren, R., and Goldstein, R.A. (1999). Estimating the total number of protein folds. Proteins: Struct. Funct. Genet. 35, 408-414.

Krogh, A., Larsson, B., von Heijne, G., Sonnhammer, E.L.L. (2001). Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes. J. Mol. Biol. 305, 567-580.

McGhee?, G.R. Theoretical morphology. The Concept and its applications. New York: Columbia University Press. 1999.

Orengo, C.A. (1994), "Classification of protein folds", Current opinion in Structural Biology 4 429-440.

Orengo, C.A. (1999). Protein folds, functions and evolution. J.Mol.Biol. 293, 333-342.

Patthy, L. (1996) Exon shuffling and other ways of module exchange. Matrix biology. 15(5), 301-310.

Ptitsyn, O.B. and Finkelstein, A.V. (1980), "Similarities of protein topologies: evolutionary divergence, functional convergence or principles of folding", Quarterly Reviews of Biophysics 13 3 339-386.

Richardson, J.S. (1977), "Beta-sheet topology and the relatedness of proteins", Nature 268 495-500. Richardson, J.S. (1981), "The anatomy and taxonomy of protein structure", Advances in Protein Chemistry 34 167-339.

Raup, D.M. and Michelson, A. 1965. Theoretical morphology of the coiled shell. Science. 147, 1294-1295.

Salem, G.M., Hutchinson, E.G., Orengo, C.A., Thornton, J.M. (1999). Correlation of observed fold frequency with the occurrence of local structural motifs. J. Mol. Biol. 287, 969-981

Thornton, J.W. and DeSalle?, R. (2000) Gene family evolution and homology: genomics meets phylogenetics. Ann. Rev. of genomics and human genetics. 1, 41-73.

Yue, K. and Dill, K.A. (2000) Constraint-based assembly of tertiary protein structures from secondary structure elements. Prot. Sci. 9, 1935-1946.

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