Agüero-Chapin Guillermin, Domínguez-Pérez Dany, Marrero-Ponce Yovani, Castillo-Mendieta Kevin, Antunes Agostinho
CIIMAR-Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos, s/n, Porto 4450-208, Portugal.
Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, s/n, Porto 4169-007, Portugal.
ACS Omega. 2024 Oct 14;9(43):43353-43367. doi: 10.1021/acsomega.4c01959. eCollection 2024 Oct 29.
Antimicrobial peptides (AMPs) have potential against antimicrobial resistance and serve as templates for novel therapeutic agents. While most AMP databases focus on terrestrial eukaryotes, marine cephalopods represent a promising yet underexplored source. This study reveals the putative reservoir of AMPs encrypted within the proteomes of cephalopod salivary glands via in silico proteolysis. A composite protein database comprising 5,412,039 canonical and noncanonical proteins from salivary apparatus of 14 cephalopod species was subjected to digestion by 5 proteases under three protocols, yielding over 9 million of nonredundant peptides. These peptides were effectively screened by a selection of 8 prediction and sequence comparative tools, including machine learning, deep learning, multiquery similarity-based models, and complex networks. The screening prioritized the antimicrobial activity while ensuring the absence of hemolytic and toxic properties, and structural uniqueness compared to known AMPs. Five relevant AMP datasets were released, ranging from a comprehensive collection of 542,485 AMPs to a refined dataset of 68,694 nonhemolytic and nontoxic AMPs. Further comparative analyses and application of network science principles helped identify 5466 unique and 808 representative nonhemolytic and nontoxic AMPs. These datasets, along with the selected mining tools, provide valuable resources for peptide drug developers.
抗菌肽（AMPs）具有对抗抗菌耐药性的潜力，可作为新型治疗药物的模板。虽然大多数AMPs数据库关注陆地真核生物，但海洋头足类动物是一个有前景但尚未充分探索的来源。本研究通过计算机模拟蛋白水解揭示了头足类动物唾液腺蛋白质组中编码的AMPs假定储存库。一个包含来自14种头足类动物唾液器官的5,412,039种典型和非典型蛋白质的复合蛋白质数据库，在三种方案下用5种蛋白酶进行消化，产生了超过900万个非冗余肽段。通过选择8种预测和序列比较工具，包括机器学习、深度学习、基于多查询相似性的模型和复杂网络，对这些肽段进行了有效筛选。筛选过程优先考虑抗菌活性，同时确保不存在溶血和毒性特性，以及与已知AMPs相比的结构独特性。发布了五个相关的AMPs数据集，范围从包含542,485个AMPs的综合集合到包含68,694个非溶血和无毒AMPs的精炼数据集。进一步的比较分析和网络科学原理的应用有助于识别出5466个独特的以及808个具有代表性的非溶血和无毒AMPs。这些数据集以及选定的挖掘工具为肽类药物开发者提供了宝贵的资源。
