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Open AccessArticle

Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations

1
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, China
2
Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong 999077, China
3
State Key Lab of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
4
Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Acton 2601, Australia
5
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the study.
Int. J. Mol. Sci. 2018, 19(3), 916; https://doi.org/10.3390/ijms19030916
Received: 19 February 2018 / Revised: 15 March 2018 / Accepted: 17 March 2018 / Published: 20 March 2018
(This article belongs to the Collection Proteins and Protein-Ligand Interactions)
A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm. The differentiated pathways for the six core residues form a dynamic network that outlines the area of structure alteration. The results offer potentials of using affordable computing power to predict allosteric structure of mutants in knowledge-based mutagenesis. View Full-Text
Keywords: ensemble allosteric model; dynamic network; cross-correlation; dynamic network pathways ensemble allosteric model; dynamic network; cross-correlation; dynamic network pathways
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MDPI and ACS Style

Mei, L.; Zhou, Y.; Zhu, L.; Liu, C.; Wu, Z.; Wang, F.; Hao, G.; Yu, D.; Yuan, H.; Cui, Y. Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations. Int. J. Mol. Sci. 2018, 19, 916.

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