Suarez-Leston Fabián, Calvelo Martin, Tolufashe Gideon F, Muñoz Alicia, Veleiro Uxía, Porto César, Bastos Margarida, Piñeiro Ángel, Garcia-Fandino Rebeca
Department of Organic Chemistry, Center for Research in Biological Chemistry and Molecular Materials, Santiago de Compostela University, CIQUS, Spain.
Departamento de Física Aplicada, Facultade de Física, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
Comput Struct Biotechnol J. 2022 Jan 31;20:874-881. doi: 10.1016/j.csbj.2022.01.025. eCollection 2022.
Host defense peptides (HDPs) are short cationic peptides that play a key role in the innate immune response of all living organisms. Their action mechanism does not depend on the presence of protein receptors, but on their ability to target and disrupt the membranes of a wide range of pathogenic and pathologic cells which are recognized by their specific compositions, typically with a relatively high concentration of anionic lipids. Lipid profile singularities have been found in cancer, inflammation, bacteria, viral infections, and even in senescent cells, enabling the possibility to use them as therapeutic targets and/or diagnostic biomarkers. Molecular dynamics (MD) simulations are extraordinarily well suited to explore how HDPs interact with membrane models, providing a large amount of qualitative and quantitative information that, nowadays, cannot be assessed by wet-lab methods at the same level of temporal and spatial resolution. Here, we present SuPepMem, an open-access repository containing MD simulations of different natural and artificial peptides with potential membrane lysis activity, interacting with membrane models of healthy mammal, bacteria, viruses, cancer or senescent cells. In addition to a description of the HDPs and the target systems, SuPepMem provides both the input files necessary to run the simulations and also the results of some selected analyses, including structural and MD-based quantitative descriptors. These descriptors are expected to be useful to train machine learning algorithms that could contribute to design new therapeutic peptides. Tools for comparative analysis between different HDPs and model membranes, as well as to restrict the queries to structural and time-averaged properties are also available. SuPepMem is a living project, that will continuously grow with more simulations including peptides of different sequences, MD simulations with different number of peptide units, more membrane models and also several resolution levels. The database is open to MD simulations from other users (after quality check by the SuPepMem team). SuPepMem is freely available under https://supepmem.com/.
宿主防御肽（HDPs）是一类短阳离子肽，在所有生物体的固有免疫反应中起关键作用。它们的作用机制不依赖于蛋白质受体的存在，而是取决于其靶向和破坏多种致病和病理细胞细胞膜的能力，这些细胞通过其特定组成被识别，通常含有相对高浓度的阴离子脂质。在癌症、炎症、细菌、病毒感染甚至衰老细胞中都发现了脂质谱的异常，这使得将它们用作治疗靶点和/或诊断生物标志物成为可能。分子动力学（MD）模拟非常适合探索HDPs与膜模型的相互作用，提供大量定性和定量信息，而目前湿实验室方法无法在相同的时间和空间分辨率水平上进行评估。在这里，我们展示了SuPepMem，这是一个开放获取的数据库，包含不同天然和人工肽与健康哺乳动物、细菌、病毒、癌症或衰老细胞的膜模型相互作用的MD模拟，这些肽具有潜在的膜裂解活性。除了对HDPs和目标系统的描述外，SuPepMem还提供运行模拟所需的输入文件以及一些选定分析的结果，包括基于结构和MD的定量描述符。这些描述符有望用于训练机器学习算法，有助于设计新的治疗性肽。还提供了用于不同HDPs和模型膜之间比较分析的工具，以及将查询限制在结构和时间平均属性的工具。SuPepMem是一个不断发展的项目，将通过更多模拟持续增长，包括不同序列的肽、不同肽单元数量的MD模拟、更多膜模型以及多个分辨率水平。该数据库对其他用户的MD模拟开放（经SuPepMem团队质量检查后）。SuPepMem可在https://supepmem.com/免费获取。
