TY - JOUR
T1 - Integrative Structural Biology in the Era of Accurate Structure Prediction
T2 - The Era of Accurate Structure Prediction
AU - Masrati, Gal
AU - Landau, Meytal
AU - Ben-Tal, Nir
AU - Lupas, Andrei
AU - Kosloff, Mickey
AU - Kosinski, Jan
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - AlphaFold2
KW - NMR
KW - X-ray crystallography
KW - cryo-electron microscopy
KW - protein conformations
KW - protein structure prediction
UR - http://www.scopus.com/inward/record.url?scp=85110767287&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2021.167127
DO - 10.1016/j.jmb.2021.167127
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C2 - 34224746
AN - SCOPUS:85110767287
SN - 0022-2836
VL - 433
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 20
M1 - 167127
ER -