Division of Computing and Software Systems, University of Washington Bothell, Bothell, WA 98011, United States.
Division of Computing and Software Systems, University of Washington Bothell, Bothell, WA 98011, United States.
J Mol Biol. 2023 May 1;435(9):167967. doi: 10.1016/j.jmb.2023.167967. Epub 2023 Jan 18.
The study of macromolecular structures has expanded our understanding of the amazing cell machinery and such knowledge has changed how the pharmaceutical industry develops new vaccines in recent years. Traditionally, X-ray crystallography has been the main method for structure determination, however, cryogenic electron microscopy (cryo-EM) has increasingly become more popular due to recent advancements in hardware and software. The number of cryo-EM maps deposited in the EMDataResource (formerly EMDatabase) since 2002 has been dramatically increasing and it continues to do so. De novo macromolecular complex modeling is a labor-intensive process, therefore, it is highly desirable to develop software that can automate this process. Here we discuss our automated, data-driven, and artificial intelligence approaches including map processing, feature extraction, modeling building, and target identification. Recently, we have enabled DNA/RNA modeling in our deep learning-based prediction tool, DeepTracer. We have also developed DeepTracer-ID, a tool that can identify proteins solely based on the cryo-EM map. In this paper, we will present our accumulated experiences in developing deep learning-based methods surrounding macromolecule modeling applications.
大分子结构的研究扩展了我们对神奇细胞机制的理解,近年来,这种知识改变了制药行业开发新疫苗的方式。传统上,X 射线晶体学一直是结构测定的主要方法,然而,由于硬件和软件的最新进展,低温电子显微镜(cryo-EM)越来越受欢迎。自 2002 年以来,EMDataResource(以前称为 EMDatabase)中储存的 cryo-EM 图谱数量急剧增加,并且这种趋势仍在继续。从头开始的大分子复合物建模是一个劳动密集型过程,因此,非常希望开发能够自动化该过程的软件。在这里,我们讨论了我们的自动化、数据驱动和人工智能方法,包括图谱处理、特征提取、建模构建和目标识别。最近,我们已经在基于深度学习的预测工具 DeepTracer 中启用了 DNA/RNA 建模。我们还开发了 DeepTracer-ID,这是一种仅基于 cryo-EM 图谱即可识别蛋白质的工具。在本文中,我们将介绍在开发基于深度学习的大分子建模应用方法方面积累的经验。