AlloReverse: multiscale understanding among hierarchical allosteric regulations

Jinyin Zha; Qian Li; Xinyi Liu; Weidong Lin; Tingting Wang; Jiacheng Wei; Ziliang Zhang; Xun Lu; Jing Wu; Duan Ni; Kun Song; Liang Zhang; Xuefeng Lu; Shaoyong Lu; Jian Zhang

doi:10.1093/nar/gkad279

AlloReverse: multiscale understanding among hierarchical allosteric regulations

Jinyin Zha (Co-first Author), Qian Li (Co-first Author), Xinyi Liu (Co-first Author), Weidong Lin (Co-first Author), Tingting Wang (Co-first Author), Jiacheng Wei, Ziliang Zhang, Xun Lu, Jing Wu, Duan Ni, Kun Song, Liang Zhang, Xuefeng Lu^*, Shaoyong Lu^*, Jian Zhang^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

23 Citations (Scopus)

68 Downloads (CityUHK Scholars)

Abstract

Increasing data in allostery are requiring analysis of coupling relationships among different allosteric sites on a single protein. Here, based on our previous efforts on reversed allosteric communication theory, we have developed AlloReverse, a web server for multiscale analysis of multiple allosteric regulations. AlloReverse integrates protein dynamics and machine learning to discover allosteric residues, allosteric sites and regulation pathways. Especially, AlloReverse could reveal hierarchical relationships between different pathways and couplings among allosteric sites, offering a whole map of allostery. The web server shows a good performance in re-emerging known allostery. Moreover, we applied AlloReverse to explore global allostery on CDC42 and SIRT3. AlloReverse predicted novel allosteric sites and allosteric residues in both systems, and the functionality of sites was validated experimentally. It also suggests a possible scheme for combined therapy or bivalent drugs on SIRT3. Taken together, AlloReverse is a novel workflow providing a complete regulation map and is believed to aid target identification, drug design and understanding of biological mechanisms. AlloReverse is freely available to all users at https://mdl.shsmu.edu.cn/AlloReverse/ or http://www.allostery.net/AlloReverse/.

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

Original language	English
Pages (from-to)	W33–W38
Journal	Nucleic acids research
Volume	51
Issue number	W1
Online published	18 Apr 2023
DOIs	https://doi.org/10.1093/nar/gkad279
Publication status	Published - 5 Jul 2023

Research Keywords

SIRT3
COMMUNICATION
MECHANISM
PROTEINS
REVEAL
SITES
STATE

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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title = "AlloReverse: multiscale understanding among hierarchical allosteric regulations",

abstract = "Increasing data in allostery are requiring analysis of coupling relationships among different allosteric sites on a single protein. Here, based on our previous efforts on reversed allosteric communication theory, we have developed AlloReverse, a web server for multiscale analysis of multiple allosteric regulations. AlloReverse integrates protein dynamics and machine learning to discover allosteric residues, allosteric sites and regulation pathways. Especially, AlloReverse could reveal hierarchical relationships between different pathways and couplings among allosteric sites, offering a whole map of allostery. The web server shows a good performance in re-emerging known allostery. Moreover, we applied AlloReverse to explore global allostery on CDC42 and SIRT3. AlloReverse predicted novel allosteric sites and allosteric residues in both systems, and the functionality of sites was validated experimentally. It also suggests a possible scheme for combined therapy or bivalent drugs on SIRT3. Taken together, AlloReverse is a novel workflow providing a complete regulation map and is believed to aid target identification, drug design and understanding of biological mechanisms. AlloReverse is freely available to all users at https://mdl.shsmu.edu.cn/AlloReverse/ or http://www.allostery.net/AlloReverse/.{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.",

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author = "Jinyin Zha and Qian Li and Xinyi Liu and Weidong Lin and Tingting Wang and Jiacheng Wei and Ziliang Zhang and Xun Lu and Jing Wu and Duan Ni and Kun Song and Liang Zhang and Xuefeng Lu and Shaoyong Lu and Jian Zhang",

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T2 - multiscale understanding among hierarchical allosteric regulations

AU - Zha, Jinyin

AU - Li, Qian

AU - Liu, Xinyi

AU - Lin, Weidong

AU - Wang, Tingting

AU - Wei, Jiacheng

AU - Zhang, Ziliang

AU - Lu, Xun

AU - Wu, Jing

AU - Ni, Duan

AU - Song, Kun

AU - Zhang, Liang

AU - Lu, Xuefeng

AU - Lu, Shaoyong

AU - Zhang, Jian

PY - 2023/7/5

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N2 - Increasing data in allostery are requiring analysis of coupling relationships among different allosteric sites on a single protein. Here, based on our previous efforts on reversed allosteric communication theory, we have developed AlloReverse, a web server for multiscale analysis of multiple allosteric regulations. AlloReverse integrates protein dynamics and machine learning to discover allosteric residues, allosteric sites and regulation pathways. Especially, AlloReverse could reveal hierarchical relationships between different pathways and couplings among allosteric sites, offering a whole map of allostery. The web server shows a good performance in re-emerging known allostery. Moreover, we applied AlloReverse to explore global allostery on CDC42 and SIRT3. AlloReverse predicted novel allosteric sites and allosteric residues in both systems, and the functionality of sites was validated experimentally. It also suggests a possible scheme for combined therapy or bivalent drugs on SIRT3. Taken together, AlloReverse is a novel workflow providing a complete regulation map and is believed to aid target identification, drug design and understanding of biological mechanisms. AlloReverse is freely available to all users at https://mdl.shsmu.edu.cn/AlloReverse/ or http://www.allostery.net/AlloReverse/.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

AB - Increasing data in allostery are requiring analysis of coupling relationships among different allosteric sites on a single protein. Here, based on our previous efforts on reversed allosteric communication theory, we have developed AlloReverse, a web server for multiscale analysis of multiple allosteric regulations. AlloReverse integrates protein dynamics and machine learning to discover allosteric residues, allosteric sites and regulation pathways. Especially, AlloReverse could reveal hierarchical relationships between different pathways and couplings among allosteric sites, offering a whole map of allostery. The web server shows a good performance in re-emerging known allostery. Moreover, we applied AlloReverse to explore global allostery on CDC42 and SIRT3. AlloReverse predicted novel allosteric sites and allosteric residues in both systems, and the functionality of sites was validated experimentally. It also suggests a possible scheme for combined therapy or bivalent drugs on SIRT3. Taken together, AlloReverse is a novel workflow providing a complete regulation map and is believed to aid target identification, drug design and understanding of biological mechanisms. AlloReverse is freely available to all users at https://mdl.shsmu.edu.cn/AlloReverse/ or http://www.allostery.net/AlloReverse/.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

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KW - COMMUNICATION

KW - MECHANISM

KW - PROTEINS

KW - REVEAL

KW - SITES

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U2 - 10.1093/nar/gkad279

DO - 10.1093/nar/gkad279

M3 - RGC 21 - Publication in refereed journal

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SN - 0305-1048

VL - 51

SP - W33–W38

JO - Nucleic acids research

JF - Nucleic acids research

IS - W1

ER -

AlloReverse: multiscale understanding among hierarchical allosteric regulations

Abstract

Research Keywords

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