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Protein Folding Absent Selection
Sequenomics LLC, 1428 Chanterelle Lane, Hillsborough, NC 27278, USA
LifeSensors Inc., 271 Great Valley Parkway, Suite 100, Malvern, PA 19355, USA
Complex Systems Center University of Vermont, 200C Farrell Hall, 210 Colchester Ave., Burlington, VT 05405, USA
* Author to whom correspondence should be addressed.
Received: 10 July 2011; in revised form: 5 August 2011 / Accepted: 11 August 2011 / Published: 16 August 2011
Abstract: Biological proteins are known to fold into specific 3D conformations. However, the fundamental question has remained: Do they fold because they are biological, and evolution has selected sequences which fold? Or is folding a common trait, widespread throughout sequence space? To address this question arbitrary, unevolved, random-sequence proteins were examined for structural features found in folded, biological proteins. Libraries of long (71 residue), random-sequence polypeptides, with ensemble amino acid composition near the mean for natural globular proteins, were expressed as cleavable fusions with ubiquitin. The structural properties of both the purified pools and individual isolates were then probed using circular dichroism, fluorescence emission, and fluorescence quenching techniques. Despite this necessarily sparse “sampling” of sequence space, structural properties that define globular biological proteins, namely collapsed conformations, secondary structure, and cooperative unfolding, were found to be prevalent among unevolved sequences. Thus, for polypeptides the size of small proteins, natural selection is not necessary to account for the compact and cooperative folded states observed in nature.
Keywords: protein folding; evolution; sequence space
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LaBean, T.H.; Butt, T.R.; Kauffman, S.A.; Schultes, E.A. Protein Folding Absent Selection. Genes 2011, 2, 608-626.
LaBean TH, Butt TR, Kauffman SA, Schultes EA. Protein Folding Absent Selection. Genes. 2011; 2(3):608-626.
LaBean, Thomas H.; Butt, Tauseef R.; Kauffman, Stuart A.; Schultes, Erik A. 2011. "Protein Folding Absent Selection." Genes 2, no. 3: 608-626.