Allostery in Its Many Disguises: From Theory to Applications

Shoshana J. Wodak; Emanuele Paci; Nikolay V. Dokholyan; Igor N. Berezovsky; Amnon Horovitz; Jing Li; Vincent J. Hilser; Ivet Bahar; John Karanicolas; Gerhard Stock; Peter Hamm; Roland H. Stote; Jerome Eberhardt; Yassmine Chebaro; Annick Dejaegere; Marco Cecchini; Jean Pierre Changeux; Peter G. Bolhuis; Jocelyne Vreede; Pietro Faccioli; Simone Orioli; Riccardo Ravasio; Le Yan; Carolina Brito; Matthieu Wyart; Paraskevi Gkeka; Ivan Rivalta; Giulia Palermo; J. Andrew McCammon; Joanna Panecka-Hofman; Rebecca C. Wade; Antonella Di Pizio; Masha Y. Niv; Ruth Nussinov; Chung Jung Tsai; Hyunbum Jang; Dzmitry Padhorny; Dima Kozakov; Tom McLeish

doi:10.1016/j.str.2019.01.003

Allostery in Its Many Disguises: From Theory to Applications

Shoshana J. Wodak^*
, Emanuele Paci
, Nikolay V. Dokholyan
, Igor N. Berezovsky
, Amnon Horovitz
, Jing Li
, Vincent J. Hilser
, Ivet Bahar
, John Karanicolas
, Gerhard Stock
, Peter Hamm
, Roland H. Stote
, Jerome Eberhardt
, Yassmine Chebaro
, Annick Dejaegere
, Marco Cecchini
, Jean Pierre Changeux
, Peter G. Bolhuis
, Jocelyne Vreede
, Pietro Faccioli

Simone Orioli, Riccardo Ravasio, Le Yan, Carolina Brito, Matthieu Wyart, Paraskevi Gkeka, Ivan Rivalta, Giulia Palermo, J. Andrew McCammon, Joanna Panecka-Hofman, Rebecca C. Wade, Antonella Di Pizio, Masha Y. Niv, Ruth Nussinov, Chung Jung Tsai, Hyunbum Jang, Dzmitry Padhorny, Dima Kozakov, Tom McLeish

^*Corresponding author for this work

Human Molecular Genetics Biochemistry

Flanders Institute for Biotechnology
University of Leeds
University of North Carolina at Chapel Hill
Pennsylvania State University
National University of Singapore
Weizmann Institute of Science
Johns Hopkins University
University of Pittsburgh
Fox Chase Cancer Center
University of Freiburg
University of Zurich
Institut de Génétique et de Biologie Moléculaire et Cellulaire
Université de Strasbourg
Collège de France
University of Amsterdam
University of Trento
Swiss Federal Institute of Technology Lausanne
University of California at Santa Barbara
Universidade Federal do Rio Grande do Sul
Sanofi-Aventis
École normale supérieure de Lyon
University of California at San Diego
University of California at Riverside
University of Warsaw
Heidelberg University
Technical University of Munich
Hebrew University of Jerusalem
National Institutes of Health
Stony Brook University
University of York

Research output: Contribution to journal › Review article › peer-review

315 Scopus citations

Abstract

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop offers an insightful overview of the understanding of the mechanistic foundations of allostery, gained from computational and experimental analyses of real protein systems and model systems. Various practical applications are illustrated.

Original language	English
Pages (from-to)	566-578
Number of pages	13
Journal	Structure
Volume	27
Issue number	4
DOIs	https://doi.org/10.1016/j.str.2019.01.003
State	Published - 2 Apr 2019

Funding

Funders	Funder number
Centre Européen pour le Calcul Atomic et Moléculaire
Narodowe Centrum Nauki
Interdisciplinary Center for Scientific Computing IWR
Universität Heidelberg
KGF
Klaus Tschira Stiftung
National Institutes of Health
European Commission
Swiss Industry Science Foundation
Partnership for Advanced Computing in Europe AISBL
Combination of Collaborative Project and Coordination and Support Actions
Horizon 2020
European Regional Development Fund	FP7-PEOPLE-2009-RG, 09ΣΥN 11-675
National Institute of General Medical Sciences	R01GM114015, R01GM123247, R01GM031749, R01GM064803, P41GM103712
National Cancer Institute	494/16, HHSN261200800001E, ISF-NSFC 2463/16
National Institute on Drug Abuse	P30DA035778
Horizon 2020 Framework Programme	720270
Engineering and Physical Sciences Research Council	EP/N031431/2
Iowa Science Foundation	2463/16
Seventh Framework Programme	256533, INFRA-2010-1.2.3
CP-CSA	RI-261600
Norges Idrettshøgskole	NIG GM31749, R01GM114015, P30DA035778, R01GM123247, R01GM064803, P41GM103712
Polish National Science Centre	2016/21/D/NZ1/02806

Keywords

Allostery
allosteric drugs
allosteric material
allosteric switches
elastic network models
energy landscape
molecular dynamics
protein conformational changes
protein function
regulation
signal transduction

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10.1016/j.str.2019.01.003

Cite this

Wodak, S. J., Paci, E., Dokholyan, N. V., Berezovsky, I. N., Horovitz, A., Li, J., Hilser, V. J., Bahar, I., Karanicolas, J., Stock, G., Hamm, P., Stote, R. H., Eberhardt, J., Chebaro, Y., Dejaegere, A., Cecchini, M., Changeux, J. P., Bolhuis, P. G., Vreede, J., ... McLeish, T. (2019). Allostery in Its Many Disguises: From Theory to Applications. Structure, 27(4), 566-578. https://doi.org/10.1016/j.str.2019.01.003

@article{7274aa664c3c4cf9bd1605842eeda6d0,

title = "Allostery in Its Many Disguises: From Theory to Applications",

abstract = "Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Europ{\'e}en de Calcul Atomique et Mol{\'e}culaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts. A collection of contributions to a recent interdisciplinary CECAM (Center Europ{\'e}en de Calcul Atomique et Mol{\'e}culaire) workshop offers an insightful overview of the understanding of the mechanistic foundations of allostery, gained from computational and experimental analyses of real protein systems and model systems. Various practical applications are illustrated.",

keywords = "Allostery, allosteric drugs, allosteric material, allosteric switches, elastic network models, energy landscape, molecular dynamics, protein conformational changes, protein function, regulation, signal transduction",

author = "Wodak, \{Shoshana J.\} and Emanuele Paci and Dokholyan, \{Nikolay V.\} and Berezovsky, \{Igor N.\} and Amnon Horovitz and Jing Li and Hilser, \{Vincent J.\} and Ivet Bahar and John Karanicolas and Gerhard Stock and Peter Hamm and Stote, \{Roland H.\} and Jerome Eberhardt and Yassmine Chebaro and Annick Dejaegere and Marco Cecchini and Changeux, \{Jean Pierre\} and Bolhuis, \{Peter G.\} and Jocelyne Vreede and Pietro Faccioli and Simone Orioli and Riccardo Ravasio and Le Yan and Carolina Brito and Matthieu Wyart and Paraskevi Gkeka and Ivan Rivalta and Giulia Palermo and McCammon, \{J. Andrew\} and Joanna Panecka-Hofman and Wade, \{Rebecca C.\} and \{Di Pizio\}, Antonella and Niv, \{Masha Y.\} and Ruth Nussinov and Tsai, \{Chung Jung\} and Hyunbum Jang and Dzmitry Padhorny and Dima Kozakov and Tom McLeish",

note = "Publisher Copyright: {\textcopyright} 2019",

year = "2019",

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doi = "10.1016/j.str.2019.01.003",

language = "אנגלית",

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Wodak, SJ, Paci, E, Dokholyan, NV, Berezovsky, IN, Horovitz, A, Li, J, Hilser, VJ, Bahar, I, Karanicolas, J, Stock, G, Hamm, P, Stote, RH, Eberhardt, J, Chebaro, Y, Dejaegere, A, Cecchini, M, Changeux, JP, Bolhuis, PG, Vreede, J, Faccioli, P, Orioli, S, Ravasio, R, Yan, L, Brito, C, Wyart, M, Gkeka, P, Rivalta, I, Palermo, G, McCammon, JA, Panecka-Hofman, J, Wade, RC, Di Pizio, A, Niv, MY, Nussinov, R, Tsai, CJ, Jang, H, Padhorny, D, Kozakov, D & McLeish, T 2019, 'Allostery in Its Many Disguises: From Theory to Applications', Structure, vol. 27, no. 4, pp. 566-578. https://doi.org/10.1016/j.str.2019.01.003

TY - JOUR

T1 - Allostery in Its Many Disguises

T2 - From Theory to Applications

AU - Wodak, Shoshana J.

AU - Paci, Emanuele

AU - Dokholyan, Nikolay V.

AU - Berezovsky, Igor N.

AU - Horovitz, Amnon

AU - Li, Jing

AU - Hilser, Vincent J.

AU - Bahar, Ivet

AU - Karanicolas, John

AU - Stock, Gerhard

AU - Hamm, Peter

AU - Stote, Roland H.

AU - Eberhardt, Jerome

AU - Chebaro, Yassmine

AU - Dejaegere, Annick

AU - Cecchini, Marco

AU - Changeux, Jean Pierre

AU - Bolhuis, Peter G.

AU - Vreede, Jocelyne

AU - Faccioli, Pietro

AU - Orioli, Simone

AU - Ravasio, Riccardo

AU - Yan, Le

AU - Brito, Carolina

AU - Wyart, Matthieu

AU - Gkeka, Paraskevi

AU - Rivalta, Ivan

AU - Palermo, Giulia

AU - McCammon, J. Andrew

AU - Panecka-Hofman, Joanna

AU - Wade, Rebecca C.

AU - Di Pizio, Antonella

AU - Niv, Masha Y.

AU - Nussinov, Ruth

AU - Tsai, Chung Jung

AU - Jang, Hyunbum

AU - Padhorny, Dzmitry

AU - Kozakov, Dima

AU - McLeish, Tom

PY - 2019/4/2

Y1 - 2019/4/2

N2 - Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop offers an insightful overview of the understanding of the mechanistic foundations of allostery, gained from computational and experimental analyses of real protein systems and model systems. Various practical applications are illustrated.

AB - Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop offers an insightful overview of the understanding of the mechanistic foundations of allostery, gained from computational and experimental analyses of real protein systems and model systems. Various practical applications are illustrated.

KW - Allostery

KW - allosteric drugs

KW - allosteric material

KW - allosteric switches

KW - elastic network models

KW - energy landscape

KW - molecular dynamics

KW - protein conformational changes

KW - protein function

KW - regulation

KW - signal transduction

UR - https://www.scopus.com/pages/publications/85063381900

U2 - 10.1016/j.str.2019.01.003

DO - 10.1016/j.str.2019.01.003

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AN - SCOPUS:85063381900

SN - 0969-2126

VL - 27

SP - 566

EP - 578

JO - Structure

JF - Structure

IS - 4

ER -

Allostery in Its Many Disguises: From Theory to Applications

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Keywords

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