美国密歇根大学Yang Zhang团队近期取得重要工作进展，他们研究开发了US-align平台，可用于蛋白质、核酸和大分子复合物的通用结构排列比对。相关论文2022年8月29日在线发表于《自然—方法学》杂志上。

研究人员开发了第一个通用平台US-align，以统一排列不同大分子（蛋白质、RNA 和DNA）的单体和复杂结构。该管道建立在统一的TM评分目标函数与启发式对齐搜索算法相结合的基础上。大规模的基准测试表明，在不同分子的成对和多重结构比对中，US-align优于最先进的方法。

详细分析表明，US-align的主要优势在于通过有效的启发式搜索迭代对统一目标函数进行了广泛的优化，从而大大提高了结构对齐过程的准确性和速度。同时，融合不同分子和结构类型的通用协议有助于促进异构寡聚体结构比较和基于模板的蛋白质-蛋白质和蛋白质-RNA/DNA对接。

据介绍，结构比较与排列比对在结构生物学研究中具有重要的意义。

附：英文原文

Title: US-align: universal structure alignments of proteins, nucleic acids, and macromolecular complexes

Author: Zhang, Chengxin, Shine, Morgan, Pyle, Anna Marie, Zhang, Yang

Issue&Volume: 2022-08-29

Abstract: Structure comparison and alignment are of fundamental importance in structural biology studies. We developed the first universal platform, US-align, to uniformly align monomer and complex structures of different macromolecules—proteins, RNAs and DNAs. The pipeline is built on a uniform TM-score objective function coupled with a heuristic alignment searching algorithm. Large-scale benchmarks demonstrated consistent advantages of US-align over state-of-the-art methods in pairwise and multiple structure alignments of different molecules. Detailed analyses showed that the main advantage of US-align lies in the extensive optimization of the unified objective function powered by efficient heuristic search iterations, which substantially improve the accuracy and speed of the structural alignment process. Meanwhile, the universal protocol fusing different molecular and structural types helps facilitate the heterogeneous oligomer structure comparison and template-based protein–protein and protein–RNA/DNA docking.

DOI: 10.1038/s41592-022-01585-1

Source: https://www.nature.com/articles/s41592-022-01585-1