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Probing Oligomerized Conformations of Defensin in the Membrane

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Computational Protein Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1529))

Abstract

Computational prediction and design of membrane protein–protein interactions facilitate biomedical engineering and biotechnological applications. Due to their antimicrobial activity, human defensins play an important role in the innate immune system. Human defensins are attractive pharmaceutical targets due to their small size, broad activity spectrum, reduced immunogenicity, and resistance to proteolysis. Protein engineering based modification of defensins can improve their pharmaceutical properties. Here we present an approach to computationally probe defensins’ oligomerization states in the membrane. First, we develop a novel docking and rescoring algorithm. Then, on the basis of the 3D structure of Sapecin, an insect defensin, and a model of its antimicrobial ion-channel, we optimize the parameters of our empirical scoring function. Finally, we apply our docking program and scoring function to the hBD-2 (human β-defensin-2) molecule and obtain structures of four possible oligomers. These results can be used in higher level simulations.

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Acknowledgments

The authors are funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was funded in part by the US Army Medical Research Acquisition Activity under grant W81XWH-05-1-0002. N.Z. thanks Chinese NFSC grant 30772529 and 973 program grants 2011CB933100 and 2010CB933900.

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Correspondence to Ruth Nussinov .

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Gan, W., Schneidman, D., Zhang, N., Ma, B., Nussinov, R. (2017). Probing Oligomerized Conformations of Defensin in the Membrane. In: Samish, I. (eds) Computational Protein Design. Methods in Molecular Biology, vol 1529. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6637-0_18

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  • DOI: https://doi.org/10.1007/978-1-4939-6637-0_18

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6635-6

  • Online ISBN: 978-1-4939-6637-0

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