Ye Rui, Xu Chen, Ding Zhong-Jie, Zheng Shao-Jian, Marrink Siewert-Jan, Zhang Dong, Zhou Ruhong
Institute of Quantitative Biology, School of Physics and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen 9747 AG, the Netherlands.
Comput Struct Biotechnol J. 2025 Mar 24;27:1296-1304. doi: 10.1016/j.csbj.2025.03.029. eCollection 2025.
Recognition of phytosulfokine (PSK), a sulfated pentapeptide, by its receptor PSKRs is crucial in regulating plant growth, development, and reproduction. However, designing highly active PSK remains a formidable challenge due to the lack of understanding of the structure-property relationship, structural dynamics, and the binding characteristics of PSK. Here, with a combined theoretical and experimental approach, we have investigated the binding dynamics of key interactions between PSK and AtPSKR1 to reveal the molecular mechanism of PSK recognition. Our molecular dynamics simulations and free energy perturbation calculations demonstrate that the sulfated tyrosines (PSK and PSK) are indispensable for forming stable PSK-AtPSKR1 complex, while the alanine substitution at PSK site is rather tolerated. Furthermore, two promising PSK peptide analogs (PSK and PSK) with enhanced biological activity have been designed through mutagenesis studies and experiments. They have a strong promoting effect (20 % enhancement) on stimulating root development compared with the wild-type PSK treatment. This work offers an effective strategy to design new peptide-based drugs for facilitating plant growth and consequent crop productivity, potentially benefiting efforts to address the global food crisis.
植物磺肽素（PSK）是一种硫酸化五肽，其受体PSKRs对它的识别在调节植物生长、发育和繁殖过程中至关重要。然而，由于对PSK的结构-性质关系、结构动力学和结合特性缺乏了解，设计高活性的PSK仍然是一项艰巨的挑战。在此，我们采用理论与实验相结合的方法，研究了PSK与AtPSKR1之间关键相互作用的结合动力学，以揭示PSK识别的分子机制。我们的分子动力学模拟和自由能扰动计算表明，硫酸化酪氨酸（PSK₁和PSK₂）对于形成稳定的PSK-AtPSKR1复合物是不可或缺的，而PSK位点的丙氨酸取代则相对可以耐受。此外，通过诱变研究和实验设计了两种具有增强生物活性的有前景的PSK肽类似物（PSK₃和PSK₄）。与野生型PSK处理相比，它们对刺激根系发育具有很强的促进作用（增强20%）。这项工作为设计促进植物生长及提高作物产量的新型肽基药物提供了一种有效策略，有望为解决全球粮食危机做出贡献。
