Protein disorder and the evolution of molecular recognition

theory, predictions and observations.

A. Dunker, E. Garner, S. Guilliot, P. Romero, K. Albrecht, J. Hart, Z. Obradovic, C. Kissinger, J. E. Villafranca

Research output: Chapter in Book/Report/Conference proceedingChapter

302 Citations (Scopus)

Abstract

Observations going back more than 20 years show that regions in proteins with disordered backbones can play roles in their binding to other molecules; typically, the disordered regions become ordered upon complex formation. Thought-experiments with Schulz Diagrams, which are defined herein, suggest that disorder-to-order transitions are required for natural selection to operate separately on affinity and specificity. Separation of affinity and specificity may be essential for fine-tuning the molecular interaction networks that comprise the living state. For low affinity, high specificity interactions, our analysis suggests that natural selection would parse the amino acids conferring flexibility in the unbound state from those conferring specificity in the bound state. For high affinity, low specificity or for high affinity, multiple specificity interactions, our analysis suggests that the disorder-to-order transitions enable alternative packing interactions between side chains to accommodate the different binding targets. Disorder-to-order transitions upon binding also have significant kinetic implications as well, by having complex effects on both on- and off-rates. Current data are insufficient to decide on these proposals, but sequence and structure analysis on two examples support further investigations of the role of disorder-to-order transitions upon binding.

Original languageEnglish (US)
Title of host publicationPacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
Pages473-484
Number of pages12
StatePublished - 1998
Externally publishedYes

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Molecular Evolution
Genetic Selection
Sequence Analysis
Proteins
Amino Acids

Cite this

Dunker, A., Garner, E., Guilliot, S., Romero, P., Albrecht, K., Hart, J., ... Villafranca, J. E. (1998). Protein disorder and the evolution of molecular recognition: theory, predictions and observations. In Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing (pp. 473-484)

Protein disorder and the evolution of molecular recognition : theory, predictions and observations. / Dunker, A.; Garner, E.; Guilliot, S.; Romero, P.; Albrecht, K.; Hart, J.; Obradovic, Z.; Kissinger, C.; Villafranca, J. E.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 1998. p. 473-484.

Research output: Chapter in Book/Report/Conference proceedingChapter

Dunker, A, Garner, E, Guilliot, S, Romero, P, Albrecht, K, Hart, J, Obradovic, Z, Kissinger, C & Villafranca, JE 1998, Protein disorder and the evolution of molecular recognition: theory, predictions and observations. in Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. pp. 473-484.
Dunker A, Garner E, Guilliot S, Romero P, Albrecht K, Hart J et al. Protein disorder and the evolution of molecular recognition: theory, predictions and observations. In Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 1998. p. 473-484
Dunker, A. ; Garner, E. ; Guilliot, S. ; Romero, P. ; Albrecht, K. ; Hart, J. ; Obradovic, Z. ; Kissinger, C. ; Villafranca, J. E. / Protein disorder and the evolution of molecular recognition : theory, predictions and observations. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 1998. pp. 473-484
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