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 FaccioliSimone 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

Research output: Contribution to journalReview articlepeer-review

236 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 languageEnglish
Pages (from-to)566-578
Number of pages13
JournalStructure
Volume27
Issue number4
DOIs
StatePublished - 2 Apr 2019

Funding

FundersFunder number
CP-CSARI-261600
Centre Européen pour le Calcul Atomic et Moléculaire
Combination of Collaborative Project and Coordination and Support Actions
Interdisciplinary Center for Scientific Computing IWR
KGF
Polish National Science Centre2016/21/D/NZ1/02806
Swiss Industry Science Foundation
National Institutes of HealthR01GM114015, R01GM123247, R01GM064803, P41GM103712
National Institutes of Health
National Institute on Drug AbuseP30DA035778
National Institute on Drug Abuse
National Cancer Institute494/16, HHSN261200800001E, GM31749, ISF-NSFC 2463/16
National Cancer Institute
Iowa Science Foundation2463/16
Iowa Science Foundation
European Commission
Heidelberg University 
Partnership for Advanced Computing in Europe AISBL
Narodowe Centrum Nauki
Seventh Framework ProgrammeINFRA-2010-1.2.3
Seventh Framework Programme
Klaus Tschira Stiftung
Horizon 2020720270
Horizon 2020
European Regional Development FundFP7-PEOPLE-2009-RG, 256533, 09ΣΥN 11-675
European Regional Development Fund
Norges IdrettshøgskoleNIG GM31749
Norges Idrettshøgskole

    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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