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J R Soc Interface. 2010 Mar 6;7(44):397-408. doi: 10.1098/rsif.2009.0193. Epub 2009 Jul 22.

Analysis of a complete DNA-protein affinity landscape.

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Manchester Interdisciplinary Biocentre, University of Manchester , 131 Princess Street, Manchester M1 7DN, UK.


Properties of biological fitness landscapes are of interest to a wide sector of the life sciences, from ecology to genetics to synthetic biology. For biomolecular fitness landscapes, the information we currently possess comes primarily from two sources: sparse samples obtained from directed evolution experiments; and more fine-grained but less authentic information from 'in silico' models (such as NK-landscapes). Here we present the entire protein-binding profile of all variants of a nucleic acid oligomer 10 bases in length, which we have obtained experimentally by a series of highly parallel on-chip assays. The resulting complete landscape of sequence-binding pairs, comprising more than one million binding measurements in duplicate, has been analysed statistically using a number of metrics commonly applied to synthetic landscapes. These metrics show that the landscape is rugged, with many local optima, and that this arises from a combination of experimental variation and the natural structural properties of the oligonucleotides.

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