Cited by 53Protein Structure and DynamicsEnzyme Structure and FunctionReceptor Mechanisms and Signaling

Integrative Structural Biology in the Era of Accurate Structure Prediction

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Masrati, Gal, Landau, Meytal, Ben-Tal, Nir, Lupas, Andrei, Kosloff, Mickey, Kosinski, Jan·2021·Journal of Molecular Biology

Abstract

Characterizing the three-dimensional structure of macromolecules is central to understanding their function. Traditionally, structures of proteins and their complexes have been determined using experimental techniques such as X-ray crystallography, NMR, or cryo-electron microscopy-applied individually or in an integrative manner. Meanwhile, however, computational methods for protein structure prediction have been improving their accuracy, gradually, then suddenly, with the breakthrough advance by AlphaFold2, whose models of monomeric proteins are often as accurate as experimental structures. This breakthrough foreshadows a new era of computational methods that can build accurate models for most monomeric proteins. Here, we envision how such accurate modeling methods can combine with experimental structural biology techniques, enhancing integrative structural biology. We highlight the challenges that arise when considering multiple structural conformations, protein complexes, and polymorphic assemblies. These challenges will motivate further developments, both in modeling programs and in methods to solve experimental structures, towards better and quicker investigation of structure-function relationships.

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  1. Demis Hassabis, Brief update on some exciting progress on #AlphaFold! We've been heads down working flat out on our full methods paper (currently under review) with accompanying open source code and on providing broad free access to AlphaFold for the scientific community. More very soon! https://t.co/uP7uzgGMSf, @demishassabis. (2021). https://twitter.com/demishassabis/status/1405922 961710854144 (accessed June 23, 2021).

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Authors
Masrati, G., Landau, M., Ben-Tal, N., Lupas, A., Kosloff, M., & Kosinski, J.
Affiliations
  • Tel Aviv University (IL)
  • Technion – Israel Institute of Technology (IL)
  • Max Planck Institute for Developmental Biology (DE)
  • University of Haifa (IL)
Corresponding author
  • Lupas, Andrei
  • Kosloff, Mickey
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2021-10
Volume
433
Issue
20
Pages
167127
ISSN
0022-2836 (ISSN-L)
OpenAlex
W3181374387
Cited by
53
References
213
Citations by year
2026: 2 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 21 · 2021: 7
FWCI
1.18
Type
journal article
Language
en
Open access
Locations
  • Journal of Molecular Biology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (submittedVersion, other-oa)
Funders
  • Max-Planck-Gesellschaft
  • Tel Aviv University
  • Canadian Institutes of Health Research
  • BMBF Berlin
  • International Development Research Centre
  • Azrieli Foundation (3512/19)
  • Israel Science Foundation
  • Bundesministerium für Bildung und Forschung (FKZ 031L0100)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
integrative structural biology, protein structure prediction, AlphaFold2, macromolecular structure determination, protein complexes, structural polymorphism, structure-function relationship
MeSH terms
Animals, Humans, Models, Molecular, Protein Conformation, Proteins, Crystallography, X-Ray, Nuclear Magnetic Resonance, Biomolecular

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