Browsing by Author "Zhou, Quan"

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    Circular permutation profiling by deep sequencing libraries created using transposon mutagenesis
    (Oxford University Press, 2018) Atkinson, Joshua T.; Jones, Alicia M.; Zhou, Quan; Silberg, Jonathan J.
    Deep mutational scanning has been used to create high-resolution DNA sequence maps that illustrate the functional consequences of large numbers of point mutations. However, this approach has not yet been applied to libraries of genes created by random circular permutation, an engineering strategy that is used to create open reading frames that express proteins with altered contact order. We describe a new method, termed circular permutation profiling with DNA sequencing (CPP-seq), which combines a one-step transposon mutagenesis protocol for creating libraries with a functional selection, deep sequencing and computational analysis to obtain unbiased insight into a protein's tolerance to circular permutation. Application of this method to an adenylate kinase revealed that CPP-seq creates two types of vectors encoding each circularly permuted gene, which differ in their ability to express proteins. Functional selection of this library revealed that >65% of the sampled vectors that express proteins are enriched relative to those that cannot translate proteins. Mapping enriched sequences onto structure revealed that the mobile AMP binding and rigid core domains display greater tolerance to backbone fragmentation than the mobile lid domain, illustrating how CPP-seq can be used to relate a protein's biophysical characteristics to the retention of activity upon permutation.
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    The value of foresight
    (Elsevier, 2017) Ernst, Philip A.; Rogers, L.C.G.; Zhou, Quan
    Suppose you have one unit of stock, currently worth 1, which you must sell before time . The Optional Sampling Theorem tells us that whatever stopping time we choose to sell, the expected discounted value we get when we sell will be 1. Suppose however that we are able to see units of time into the future, and base our stopping rule on that; we should be able to do better than expected value 1. But how much better can we do? And how would we exploit the additional information? The optimal solution to this problem will never be found, but in this paper we establish remarkably close bounds on the value of the problem, and we derive a fairly simple exercise rule that manages to extract most of the value of foresight.