Integrative Structural Biology in the Era of Accurate Structure Prediction. Issue 20 (1st October 2021)

• Record Type: Journal Article
• Authors: Masrati, Gal; Landau, Meytal; Ben-Tal, Nir; Lupas, Andrei; Kosloff, Mickey; Kosinski, Jan
• Is Part Of: Journal of molecular biology. Volume 433:Issue 20(2021)
• Publication Date: 2021-10-01
• Subjects: AlphaFold2 -- protein structure prediction -- protein conformations -- X-ray crystallography -- NMR -- cryo-electron microscopy; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167127
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: New methods can model monomeric proteins accurately. Such models will enhance experimental structure determination. Experimental methods can benefit from modeling multiple alternative conformations. Accurate modeling will enhance experimental structure–function and mechanistic studies. 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.