title: The robustness and innovability of protein folds.
abstract: Assignment of protein folds to functions indicates that >60% of folds carry out one or two enzymatic functions, while few folds, for example, the TIM-barrel and Rossmann folds, exhibit hundreds. Are there structural features that make a fold amenable to functional innovation (innovability)? Do these features relate to robustness--the ability to readily accumulate sequence changes? We discuss several hypotheses regarding the relationship between the architecture of a protein and its evolutionary potential. We describe how, in a seemingly paradoxical manner, opposite properties, such as high stability and rigidity versus conformational plasticity and structural order versus disorder, promote robustness and/or innovability. We hypothesize that polarity--differentiation and low connectivity between a protein's scaffold and its active-site--is a key prerequisite for innovability.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Agnes
authors.initials: A
authors.lastname: Tóth-Petróczy
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: dan.tawfik@weizmann.ac.il.
authors.forename: Dan S
authors.initials: DS
authors.lastname: Tawfik
mesh_terms: D020134:Catalytic Domain; D019143:Evolution, Molecular; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins