Proposed mechanism for stability of proteins to evolutionary mutations.
It is shown that the sequence-ordering tendencies induced by design into different fast-folding, thermally stable native structures interfere. This interference results in a type of quasiorthogonality between optimal native structures, which divides sequence space into fast-folding, thermally stable families surrounded by slow-folding, low stability shells. A concrete example of this effect is provided by using a simple alpha carbon type model in which a complete correspondence is established between sequence and structure. It is speculated that gaps can occur in the space of protein-like sequences separating the sequence families and resulting in a mechanism for stability and diversity of protein sequence information.
Nelson
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ED
Departments of Chemistry and Physics, University of California at San Diego, La Jolla, CA 92093, USA. enelson@sdsc.edu
Onuchic
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JN
D019143:Evolution, Molecular; D006860:Hydrogen Bonding; D008956:Models, Chemical; D009154:Mutation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
D011506:Proteins