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

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-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
JournalJournal of Molecular Biology
Issue number20
StatePublished - 1 Oct 2021


FundersFunder number
Abraham E. Kazan Chair
DS Research Center at the University of Haifa
Canadian Institutes of Health Research
International Development Research Centre
Bundesministerium für Bildung und ForschungFKZ 031L0100
Israel Science Foundation
Tel Aviv University
Azrieli Foundation3512/19


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


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