Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel; European Molecular Biology Laboratory (EMBL), Hamburg 22607, Germany.
J Mol Biol. 2021 Oct 1;433(20):167127. doi: 10.1016/j.jmb.2021.167127. Epub 2021 Jul 3.
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.
研究大分子的三维结构是理解其功能的核心。传统上，蛋白质及其复合物的结构是通过 X 射线晶体学、NMR 或冷冻电子显微镜等实验技术来确定的，这些技术可以单独使用，也可以综合使用。然而，蛋白质结构预测的计算方法一直在提高其准确性，逐渐地，然后突然地，随着 AlphaFold2 的突破，其单体蛋白质的模型通常与实验结构一样准确。这一突破预示着一个新的计算方法时代，可以为大多数单体蛋白质建立准确的模型。在这里，我们设想这种准确的建模方法如何与实验结构生物学技术相结合，增强综合结构生物学。我们强调了在考虑多种结构构象、蛋白质复合物和多态组装时出现的挑战。这些挑战将推动建模程序和解决实验结构方法的进一步发展，以更好、更快地研究结构-功能关系。
