Pratyush Pawel, Kc Dukka B
Computer Science Department, Michigan Technological University, Houghton, MI, USA.
Computer Science Department, Rochester Institute of Technology, Henrietta, NY, USA.
Methods Mol Biol. 2025;2870:117-151. doi: 10.1007/978-1-0716-4213-9_8.
Posttranslational modifications (PTMs) play a crucial role in modulating the structure, function, localization, and interactions of proteins, with many PTMs being localized within supersecondary structures, such as helical pairs. These modifications can significantly influence the conformation and stability of these structures. For instance, phosphorylation introduces negative charges that alter electrostatic interactions, while acetylation or methylation of lysine residues affects the stability and interactions of alpha helices or beta strands. Given the pivotal role of supersecondary structures in the overall protein architecture, their modulation by PTMs is essential for protein functionality. This chapter explores the latest advancements in predicting sites for the five PTMs (phosphorylation, acetylation, glycosylation, methylation, and ubiquitination) known to be localized within supersecondary structures. The chapter highlights the recent advances in the prediction of these PTM sites, including the use of global contextualized embeddings from protein language models, integration of structural information, utilization of reliable positive and negative sites, and application of contrastive learning. These methodologies and emerging trends offer a roadmap for novel innovations in addressing PTM prediction challenges, particularly those linked to supersecondary structures.
翻译后修饰（PTMs）在调节蛋白质的结构、功能、定位和相互作用方面起着至关重要的作用，许多翻译后修饰位于超二级结构内，如螺旋对。这些修饰可显著影响这些结构的构象和稳定性。例如，磷酸化引入负电荷，改变静电相互作用，而赖氨酸残基的乙酰化或甲基化影响α螺旋或β链的稳定性和相互作用。鉴于超二级结构在整体蛋白质结构中的关键作用，翻译后修饰对其进行调节对于蛋白质功能至关重要。本章探讨了预测已知位于超二级结构内的五种翻译后修饰（磷酸化、乙酰化、糖基化、甲基化和泛素化）位点的最新进展。本章重点介绍了这些翻译后修饰位点预测的最新进展，包括使用来自蛋白质语言模型的全局上下文嵌入、结构信息的整合、可靠的正位点和负位点的利用以及对比学习的应用。这些方法和新趋势为应对翻译后修饰预测挑战，特别是与超二级结构相关的挑战，提供了新创新的路线图。
