Integrative Structural Biology in the Era of Accurate Structure Prediction: The Era of Accurate Structure Prediction

Gal Masrati, Meytal Landau, Nir Ben-Tal, Andrei Lupas, Mickey Kosloff, Jan Kosinski

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number167127
Pages (from-to)1-16
JournalJournal of Molecular Biology
Issue number20
StatePublished - 1 Oct 2021

Bibliographical note

Funding Information:
NB-T acknowledges the support of Grant 450/16 of the Israeli Science Foundation (ISF) and Abraham E. Kazan Chair in Structural Biology, Tel Aviv University. AL was supported by institutional funds from the Max Planck Society. MK was supported by funding from the Canadian Institutes of Health Research (CIHR), the International Development Research Centre (IDRC), the Israel Science Foundation (ISF), and the Azrieli Foundation (grant number 3512/19), the NSF-BSF (grant number 2020627), and the DS Research Center at the University of Haifa. JK was supported by funding from the Federal Ministry of Education and Research of Germany (FKZ 031L0100).

Publisher Copyright:
© 2021 The Authors


  • AlphaFold2
  • NMR
  • X-ray crystallography
  • cryo-electron microscopy
  • protein conformations
  • protein structure prediction

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology


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