Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, 100025, Taiwan.
Nat Commun. 2022 Jan 10;13(1):102. doi: 10.1038/s41467-021-27655-0.
The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/ .
功能性肽的系统设计具有技术和治疗应用。然而，需要基于模式的搜索引擎来帮助在原始序列中定位所需的功能基序，而无需考虑它们的进化保守性。现有的数据库，如蛋白质二级结构数据库 (PSS)，已经不再适用于社区，而蛋白质二级结构词典 (DSSP) 在提供蛋白质的三级结构时注释二级结构。在这里，我们从 PDB 中提取了 170 万个螺旋，并将它们编译成一个数据库（治疗性肽设计数据库；TP-DB），允许对复合模式进行查询，以方便识别螺旋结构的序列基序。我们展示了 TP-DB 如何帮助我们识别一种已知的纯化标签特异性抗体，该抗体可以重新用于幽门螺杆菌的诊断试剂盒。我们还展示了如何使用该数据库设计一种新的抗菌肽，它比其模板同源物具有更好的白色念珠菌清除率和更低的溶血率。最后，我们展示了 TP-DB 如何建议在螺旋肽抑制剂中进行点突变，以防止靶向的肿瘤发生蛋白-蛋白相互作用。TP-DB 可在 http://dyn.life.nthu.edu.tw/design/ 获得。
