Allostery in Its Many Disguises: From Theory to Applications

Shoshana J. Wodak (1) , Emanuele Paci (2) , Nikolay Dokholyan (3) , Igor Berezovsky (4) , Amnon Horovitz (5) , Jing Li (6) , Vincent Hilser (6) , Ivet Bahar (7) , John Karanicolas , Gerhard Stock , Peter Hamm , Roland H. Stote (8) , Jerome Eberhardt (8) , Yassmine Chebaro (8) , Annick Dejaegere (8) , Marco Cecchini (9) , Jean-Pierre Changeux (10, 11) , Peter Bolhuis (12) , Jocelyne Vreede (12) , Pietro Faccioli (13) , Simone Orioli (13) , Riccardo Ravasio (14) , Le Yan (15) , Carolina Brito (16) , Matthieu Wyart (14) , Paraskevi Gkeka (17) , Ivan Rivalta (18) , Giulia Palermo (19) , J. Andrew Mccammon , Joanna Panecka-Hofman , Rebecca C. Wade (20) , Antonella Di Pizio , Masha Niv , Ruth Nussinov (21) , Chung-Jung Tsai , Hyunbum Jang , Dzmitry Padhorny (22) , Dima Kozakov (22) , Tom Mcleish (23)

1 VIB-VUB Center for Structural Biology [Bruxelles]
2 University of Leeds
3 UNC - University of North Carolina at Chapel Hill [NC, USA]
4 NUS - National University of Singapore
5 Weizmann Institute of Science [Rehovot, Israël]
6 JHU - Johns Hopkins University
7 PITT - University of Pittsburgh
8 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
9 Institut de Chimie de Strasbourg
10 IP - Institut Pasteur [Paris]
11 CdF (institution) - Collège de France
12 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
13 Physics Department and INFN
14 EPFL - Ecole Polytechnique Fédérale de Lausanne
15 UC Santa Barbara - University of California [Santa Barbara]
16 UFRGS - Universidade Federal do Rio Grande do Sul [Porto Alegre]
17 Sanofi Aventis R&D [Chilly-Mazarin]
18 LC - Laboratoire de Chimie - UMR5182
19 UC Riverside - University of California [Riverside]
20 Molecular and Cellular Modeling Group
21 Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory
22 SBU - Stony Brook University [SUNY]
23 University of York [York, UK]

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.

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

Domaines: Bio-Informatique, Biologie Systémique [q-bio.QM]; Chimie théorique et/ou physique

Shoshana J. Wodak, Emanuele Paci, Nikolay Dokholyan, Igor Berezovsky, Amnon Horovitz, et al.. Allostery in Its Many Disguises: From Theory to Applications. Structure, 2019, 27 (4), pp.566-578. ⟨10.1016/j.str.2019.01.003⟩. ⟨hal-02388649⟩