基于Ssa1/2的Hst-5的计算机辅助合理修饰及其衍生物对念珠菌的抗真菌活性
{"_":"Computer-Aided Rational Modification of Hst 5 Based on Ssa1/2 and the Antifungal Activity of the Derivatives against .","i":["Candida spp"]}
摘要(中文译文)
天然抗真菌肽Histatin 5（Hst 5）是一种由人唾液腺分泌的富含组氨酸的阳离子肽，是口腔固有免疫的关键组分，但其活性中等，限制了临床应用。Hst 5通过膜受体Ssa1/2进入。本研究整合人工智能辅助与计算机辅助药物设计，对Hst 5的序列结构进行理性改造。利用ESM2-AFPpred筛选Hst 5的截短衍生物以评估其抗菌潜力，并将高概率候选物与Ssa1/2进行分子对接。鉴定出Hst 5-22，随后基于丙氨酸扫描对其进行重新设计，获得优化衍生物Hst 5-22-RW。与Hst 5相比，Hst 5-22-RW序列更短、与Ssa1/2结合更强，且抗真菌活性提高。其对氟康唑耐药菌株也表现出更优活性。RT-qPCR和跨膜追踪证实其在菌体内具有更高的细胞转运效率。CADD/AIDD驱动的优化成功获得了高活性抗真菌肽Hst 5-22-RW，为抗菌肽的理性改造提供了新策略。
Abstract
The natural antifungal peptide Histatin 5 (Hst 5) is a histidine-rich cationic peptide secreted by human salivary glands and a key component of oral innate immunity, but its moderate activity limits clinical use. Hst 5 enters via the membrane receptor Ssa1/2. Here, we integrated artificial intelligence-assisted and computer-aided drug design to rationally modified the sequence structure of Hst 5. Truncated derivatives of Hst5 were screened for antimicrobial potential using ESM2-AFPpred, and high-probability candidates were docked with Ssa1/2. The Hst 5-22 was identified, then redesigned based on alanine scanning to yield the optimized derivative Hst 5-22-RW. Compared with Hst 5, Hst 5-22-RW has a shorter sequence, stronger Ssa1/2 binding, and improved activity against . It also shows superior activity against fluconazole-resistant strains. RT-qPCR and transmembrane tracking confirmed higher cellular transport efficiency in . The CADD/AIDD-driven optimization successfully generated the highly active antifungal peptide Hst 5-22-RW, providing a novel strategy for rational modification of antimicrobial peptides.
如何引用
AMA
Yiqing Sun, Ruifang Li, Kedong Yin, Jinhua Zhang, Ruiling Zhang, Tianyi Wang, et al. {"_":"Computer-Aided Rational Modification of Hst 5 Based on Ssa1/2 and the Antifungal Activity of the Derivatives against .","i":["Candida spp"]}. Journal of medicinal chemistry. 2026; doi:10.1021/acs.jmedchem.5c03652.
APA
Yiqing Sun, Ruifang Li, Kedong Yin, Jinhua Zhang, Ruiling Zhang, Tianyi Wang, et al (2026). {"_":"Computer-Aided Rational Modification of Hst 5 Based on Ssa1/2 and the Antifungal Activity of the Derivatives against .","i":["Candida spp"]}. Journal of medicinal chemistry. https://doi.org/10.1021/acs.jmedchem.5c03652
GB/T 7714
Yiqing Sun, Ruifang Li, Kedong Yin, Jinhua Zhang, Ruiling Zhang, Tianyi Wang, et al. {"_":"Computer-Aided Rational Modification of Hst 5 Based on Ssa1/2 and the Antifungal Activity of the Derivatives against .","i":["Candida spp"]}[J]. Journal of medicinal chemistry, 2026 doi:10.1021/acs.jmedchem.5c03652.
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