Journal of Molecular Evolution

, Volume 73, Issue 3–4, pp 166–180 | Cite as

Amphiphilic α-Helical Potential: A Putative Folding Motif Adding Few Constraints to Protein Evolution



Evidence from a number of studies indicates that protein folding is dictated not only by factors stabilizing the native state, but also by potentially independent factors that create folding pathways. How natural selection might cope simultaneously with two independent factors was addressed in this study within the framework of the “Lim-model” of protein folding, which postulates that the early stages of folding of all globular proteins, regardless of their native structure, are directed at least in part by potential to form amphiphilic α-helices. For this purpose, the amphiphilic α-helical potential in randomly ordered amino acid sequences and the conservation in phylogeny of amphiphilic α-helical potential within various proteins were assessed. These analyses revealed that amphiphilic α-helical potential is a common occurrence in random sequences, and that the presence of amphiphilic α-helical potential is present but not conserved in phylogeny within a given protein. The results suggest that the rapid formation of molten globules and the variable behavior of those globules depending on the protein may be a fundamental property of polymers of naturally occurring amino acids more so than a trait that must be derived or maintained by natural selection. Further, the results point toward the utility of randomly occurring process in protein function and evolution, and suggest that the formation of efficient pathways that determine early processes in protein folding, unlike the formation of stable, native protein structure, does not present a substantial hurdle during the evolution of amino acid sequences.


Protein folding Helical intermediate Evolution Amphiphilic Randomly occurring processes Trifluoroethanol (TFE) 



The authors thank Alvin W. Lee for help writing the programs, and César Meza-Coronel for help with the figures. The authors also thank Eefei Chen and Dawn E. Bowles for helpful discussion. This study was supported in part by the Fannie E. Rippel foundation, and in part by the Howard Hughes Precollege Research Initiative at Duke University.


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of SurgeryDuke University Medical CenterDurhamUSA

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