Artificial intelligence for natural product drug discovery.

Journal: Nature reviews. Drug discovery
Published Date: Sep 11, 2023

Abstract

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to exciting developments in the computational drug design field, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature. We also discuss how to address key challenges in realizing the potential of these synergies, such as the need for high-quality datasets to train deep learning algorithms and appropriate strategies for algorithm validation.

Authors

  • Michael W Mullowney
    Duchossois Family Institute, The University of Chicago, Chicago, IL, USA.
  • Katherine R Duncan
    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
  • Somayah S Elsayed
    Department of Molecular Biotechnology, Institute of Biology, Leiden University, Leiden, The Netherlands.
  • Neha Garg
    School of Chemistry and Biochemistry, Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, GA, USA.
  • Justin J J van der Hooft
    Bioinformatics Group, Wageningen University, Wageningen, The Netherlands. justin.vanderhooft@wur.nl.
  • Nathaniel I Martin
    Biological Chemistry Group, Institute of Biology, Leiden University, Leiden, The Netherlands.
  • David Meijer
    Bioinformatics Group, Wageningen University, Wageningen, The Netherlands.
  • Barbara R Terlouw
    Bioinformatics Group, Wageningen University, Wageningen, Droevendaalsesteeg 1, 6708 PB, The Netherlands.
  • Friederike Biermann
    Bioinformatics Group, Wageningen University, Wageningen, The Netherlands.
  • Kai Blin
    The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
  • Janani Durairaj
    Bioinformatics Group, Department of Plant Sciences, Wageningen University and Research, Wageningen, The Netherlands.
  • Marina Gorostiola González
    Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
  • Eric J N Helfrich
    Institute of Molecular Bio Science, Goethe-University Frankfurt, Frankfurt am Main, Germany.
  • Florian Huber
    Centre for Digitalization and Digitality (ZDD), University of Applied Sciences Düsseldorf, Düsseldorf, Germany. florian.huber@hs-duesseldorf.de.
  • Stefan Leopold-Messer
    Institut für Mikrobiologie, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland.
  • Kohulan Rajan
    Institute for Inorganic and Analytical Chemistry, Friedrich Schiller University Jena, Lessingstr. 8, 07743 Jena, Germany.
  • Tristan de Rond
    School of Chemical Sciences, University of Auckland, Auckland, New Zealand.
  • Jeffrey A van Santen
    Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
  • Maria Sorokina
    Institute for Inorganic and Analytical Chemistry, Friedrich-Schiller University, Jena, Germany.
  • Marcy J Balunas
    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
  • Mehdi A Beniddir
    Équipe "Chimie des Substances Naturelles" Université Paris-Saclay, CNRS, BioCIS, 5 rue J.-B. Clément, 92290 Châtenay-Malabry, France. pierre.le-pogam-alluard@universite-paris-saclay.fr.
  • Doris A van Bergeijk
    Department of Molecular Biotechnology, Institute of Biology, Leiden University, Leiden, The Netherlands.
  • Laura M Carroll
    Structural and Computational Biology Unit, EMBL, Heidelberg, Germany.
  • Chase M Clark
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
  • Djork-Arné Clevert
    Department of Bioinformatics , Bayer AG , Berlin , Germany . Email: robin.winter@bayer.com.
  • Chris A Dejong
    Adapsyn Bioscience, Hamilton, Ontario, Canada.
  • Chao Du
  • Scarlet Ferrinho
    Chemistry Department, University of St Andrews, St Andrews, UK.
  • Francesca Grisoni
    Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, CH-, 8093, Zurich, Switzerland.
  • Albert Hofstetter
    Laboratory of Physical Chemistry, ETH Zürich, Zürich, Switzerland.
  • Willem Jespers
    Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
  • Olga V Kalinina
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany.
  • Satria A Kautsar
    Department of Chemistry, Scripps Research, FL, USA.
  • Hyunwoo Kim
    College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University Seoul, Goyang-si, Republic of Korea.
  • Tiago F Leao
    Center for Nuclear Energy in Agriculture, University of São Paulo, Piracicaba, Brazil.
  • Joleen Masschelein
    Center for Microbiology, VIB-KU Leuven, Heverlee, Belgium.
  • Evan R Rees
    Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
  • Raphael Reher
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
  • Daniel Reker
    Swiss Federal Institute of Technology (ETH), Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland.
  • Philippe Schwaller
    Laboratory of Artificial Chemical Intelligence (LIAC) & National Centre of Competence in Research (NCCR) Catalysis, École Polytechnique Fédérale de Lausanne Lausanne Switzerland.
  • Marwin Segler
    Microsoft Research AI4Science, Cambridge CB1 2FB, U.K.
  • Michael A Skinnider
    Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. michael.skinnider@msl.ubc.ca.
  • Allison S Walker
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, United States.
  • Egon L Willighagen
    Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, Netherlands.
  • Barbara Zdrazil
    Division of Drug Design and Medicinal Chemistry, Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, 1090, Vienna, Austria. barbara.zdrazil@univie.ac.at.
  • Nadine Ziemert
    Interfaculty Institute for Microbiology and Infection Medicine Tuebingen (IMIT), Institute for Bioinformatics and Medical Informatics (IBMI), University of Tuebingen, Tuebingen, Germany.
  • Rebecca J M Goss
    Chemistry Department, University of St Andrews, St Andrews, UK.
  • Pierre Guyomard
    Bonsai team, CRIStAL - Centre de Recherche en Informatique Signal et Automatique de Lille, Université de Lille, Villeneuve d'Ascq Cedex, France.
  • Andrea Volkamer
    In silico Toxicology and Structural Bioinformatics, Institute of Physiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. andrea.volkamer@charite.de.
  • William H Gerwick
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, La Jolla, California, 92037, United States of America. wgerwick@ucsd.edu.
  • Hyun Uk Kim
    Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea.
  • Rolf Müller
    Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University , 66123 Saarbrücken, Germany.
  • Gilles P van Wezel
    Department of Molecular Biotechnology, Institute of Biology, Leiden University, Leiden, The Netherlands.
  • Gerard J P van Westen
    Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands. Electronic address: gerard@lacdr.leidenuniv.nl.
  • Anna K H Hirsch
    Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany. anna.hirsch@helmholtz-hips.de.
  • Roger G Linington
    Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada. rliningt@sfu.ca.
  • Serina L Robinson
    Department of Environmental Microbiology, Eawag - Swiss Federal Institute for Aquatic Science and Technology, Dübendorf, Switzerland.
  • Marnix H Medema
    Bioinformatics Group, Wageningen University, Wageningen, The Netherlands. marnix.medema@wur.nl.

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