GPCRmd uncovers the dynamics of the 3D-GPCRome

Ismael Rodríguez-Espigares^#¹, Mariona Torrens-Fontanals^#¹, Johanna K S Tiemann^{2

3}, David Aranda-García¹, Juan Manuel Ramírez-Anguita¹, Tomasz Maciej Stepniewski¹, Nathalie Worp¹, Alejandro Varela-Rial^{4

5}, Adrián Morales-Pastor¹, Brian Medel-Lacruz¹, Gáspár Pándy-Szekeres⁶, Eduardo Mayol⁷, Toni Giorgino^{8

9}, Jens Carlsson¹⁰, Xavier Deupi^{11

12}, Slawomir Filipek¹³, Marta Filizola¹⁴, José Carlos Gómez-Tamayo⁷, Angel Gonzalez⁷, Hugo Gutiérrez-de-Terán¹⁵, Mireia Jiménez-Rosés⁷, Willem Jespers¹⁵, Jon Kapla¹⁰, George Khelashvili^{16

17}, Peter Kolb¹⁸, Dorota Latek¹³, Maria Marti-Solano^{18

19}, Pierre Matricon¹⁰, Minos-Timotheos Matsoukas^{7

20}, Przemyslaw Miszta¹³, Mireia Olivella⁷, Laura Perez-Benito⁷, Davide Provasi¹⁴, Santiago Ríos⁷, Iván R Torrecillas⁷, Jessica Sallander¹⁵, Agnieszka Sztyler¹³, Silvana Vasile¹⁵, Harel Weinstein^{16

17}, Ulrich Zachariae^{21

22}, Peter W Hildebrand^{2

3

23}, Gianni De Fabritiis^{4

5}, Ferran Sanz¹, David E Gloriam⁶, Arnau Cordomi⁷, Ramon Guixà-González^{24

25}, Jana Selent²⁶

Affiliations

¹ Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute-Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.
² Institute of Medical Physics and Biophysics, Charite University Medicine Berlin, Berlin, Germany.
³ Institute of Medical Physics and Biophysics, Medical University Leipzig, Leipzig, Sachsen, Germany.
⁴ Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Barcelona, Spain.
⁵ Acellera, Barcelona, Spain.
⁶ Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
⁷ Laboratori de Medicina Computacional, Unitat de Bioestadistica, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
⁸ Biophysics Institute, National Research Council of Italy, Milan, Italy.
⁹ Department of Biosciences, University of Milan, Milan, Italy.
¹⁰ Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
¹¹ Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), Villigen PSI, Switzerland.
¹² Condensed Matter Theory Group, PSI, Villigen PSI, Switzerland.
¹³ Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
¹⁴ Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁵ Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Uppsala, Sweden.
¹⁶ Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY, USA.
¹⁷ Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, NY, USA.
¹⁸ Department of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, Germany.
¹⁹ MRC Laboratory of Molecular Biology, Cambridge, UK.
²⁰ Department of Pharmacy, University of Patras, Patras, Greece.
²¹ Computational Biology, School of Life Sciences, University of Dundee, Dundee, UK.
²² Physics, School of Science and Engineering, University of Dundee, Dundee, UK.
²³ Berlin Institute of Health, Berlin, Germany.
²⁴ Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), Villigen PSI, Switzerland. ramon.guixa@psi.ch.
²⁵ Condensed Matter Theory Group, PSI, Villigen PSI, Switzerland. ramon.guixa@psi.ch.
²⁶ Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute-Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain. jana.selent@upf.edu.

^# Contributed equally.

PMID: 32661425
DOI: 10.1038/s41592-020-0884-y

GPCRmd uncovers the dynamics of the 3D-GPCRome

Ismael Rodríguez-Espigares et al. Nat Methods. 2020 Aug.

. 2020 Aug;17(8):777-787.

doi: 10.1038/s41592-020-0884-y. Epub 2020 Jul 13.

Authors

Affiliations

¹ Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute-Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain.
² Institute of Medical Physics and Biophysics, Charite University Medicine Berlin, Berlin, Germany.
³ Institute of Medical Physics and Biophysics, Medical University Leipzig, Leipzig, Sachsen, Germany.
⁴ Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, Barcelona, Spain.
⁵ Acellera, Barcelona, Spain.
⁶ Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
⁷ Laboratori de Medicina Computacional, Unitat de Bioestadistica, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
⁸ Biophysics Institute, National Research Council of Italy, Milan, Italy.
⁹ Department of Biosciences, University of Milan, Milan, Italy.
¹⁰ Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
¹¹ Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), Villigen PSI, Switzerland.
¹² Condensed Matter Theory Group, PSI, Villigen PSI, Switzerland.
¹³ Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
¹⁴ Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁵ Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Uppsala, Sweden.
¹⁶ Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY, USA.
¹⁷ Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University, New York, NY, USA.
¹⁸ Department of Pharmaceutical Chemistry, Philipps-University Marburg, Marburg, Germany.
¹⁹ MRC Laboratory of Molecular Biology, Cambridge, UK.
²⁰ Department of Pharmacy, University of Patras, Patras, Greece.
²¹ Computational Biology, School of Life Sciences, University of Dundee, Dundee, UK.
²² Physics, School of Science and Engineering, University of Dundee, Dundee, UK.
²³ Berlin Institute of Health, Berlin, Germany.
²⁴ Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), Villigen PSI, Switzerland. ramon.guixa@psi.ch.
²⁵ Condensed Matter Theory Group, PSI, Villigen PSI, Switzerland. ramon.guixa@psi.ch.
²⁶ Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute-Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona, Spain. jana.selent@upf.edu.

^# Contributed equally.

PMID: 32661425
DOI: 10.1038/s41592-020-0884-y

Erratum in

Publisher Correction: GPCRmd uncovers the dynamics of the 3D-GPCRome.
Rodríguez-Espigares I, Torrens-Fontanals M, Tiemann JKS, Aranda-García D, Ramírez-Anguita JM, Stepniewski TM, Worp N, Varela-Rial A, Morales-Pastor A, Medel-Lacruz B, Pándy-Szekeres G, Mayol E, Giorgino T, Carlsson J, Deupi X, Filipek S, Filizola M, Gómez-Tamayo JC, Gonzalez A, Gutiérrez-de-Terán H, Jiménez-Rosés M, Jespers W, Kapla J, Khelashvili G, Kolb P, Latek D, Marti-Solano M, Matricon P, Matsoukas MT, Miszta P, Olivella M, Perez-Benito L, Provasi D, Ríos S, R Torrecillas I, Sallander J, Sztyler A, Vasile S, Weinstein H, Zachariae U, Hildebrand PW, De Fabritiis G, Sanz F, Gloriam DE, Cordomi A, Guixà-González R, Selent J. Rodríguez-Espigares I, et al. Nat Methods. 2020 Aug;17(8):861-862. doi: 10.1038/s41592-020-0928-3. Nat Methods. 2020. PMID: 32704182

Abstract

G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.

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References

1. Hauser, A. S., Attwood, M. M., Rask-Andersen, M., Schiöth, H. B. & Gloriam, D. E. Trends in GPCR drug discovery: mew agents, targets and indications. Nat. Rev. Drug Discov. 16, 829–842 (2017). - PubMed - PMC
1. Munk, C. et al. GPCRdb in 2018: adding GPCR structure models and ligands. Nucleic Acids Res. 46, 440–446 (2017).
1. Munk, C. et al. An online resource for GPCR structure determination and analysis. Nat. Methods 16, 151–162 (2019). - DOI
1. Latorraca, N. R., Venkatakrishnan, A. J. & Dror, R. O. GPCR dynamics: structures in motion. Chem. Rev. 117, 139–155 (2017). - DOI
1. Hildebrand, P. W., Rose, A. S. & Tiemann, J. K. S. Bringing molecular dynamics simulation data into view. Trends Biochem. Sci. 44, 902–913 (2019). - DOI

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GPCRmd uncovers the dynamics of the 3D-GPCRome

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GPCRmd uncovers the dynamics of the 3D-GPCRome

Authors

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Abstract

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