Department of Structural Biology and Center of Excellence for Data Driven Discovery, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Department of Structural Biology and Center of Excellence for Data Driven Discovery, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. Electronic address: https://twitter.com/DucMalinverni.
Curr Opin Struct Biol. 2023 Jun;80:102608. doi: 10.1016/j.sbi.2023.102608. Epub 2023 May 12.
Recent advances in computational approaches and their integration into structural biology enable tackling increasingly complex questions. Here, we discuss several key areas, highlighting breakthroughs and remaining challenges. Theoretical modeling has provided tools to accurately predict and design protein structures on a scale currently difficult to achieve using experimental approaches. Molecular Dynamics simulations have become faster and more precise, delivering actionable information inaccessible by current experimental methods. Virtual screening workflows allow a high-throughput approach to discover ligands that bind and modulate protein function, while Machine Learning methods enable the design of proteins with new functionalities. Integrative structural biology combines several of these approaches, pushing the frontiers of structural and functional characterization to ever larger systems, advancing towards a complete understanding of the living cell. These breakthroughs will accelerate and significantly impact diverse areas of science.
计算方法的最新进展及其在结构生物学中的整合使我们能够解决越来越复杂的问题。在这里,我们讨论了几个关键领域,强调了突破和仍然存在的挑战。理论建模提供了工具,可以在当前难以通过实验方法实现的规模上准确预测和设计蛋白质结构。分子动力学模拟变得更快、更精确,提供了当前实验方法无法获得的可行信息。虚拟筛选工作流程允许采用高通量方法来发现与蛋白质相互作用并调节其功能的配体,而机器学习方法则可以设计具有新功能的蛋白质。综合结构生物学结合了这些方法中的几种,将结构和功能表征的前沿推向更大的系统,朝着对活细胞的全面理解迈进。这些突破将加速并显著影响科学的各个领域。