25-Hydroxycholesterol (25HC), one of the most important oxysterol molecules, can be used by cells to fight bacterial and viral infections but the mechanism that defines its biological effects are unknown. Using molecular dynamics, we have aimed to describe the orientation and location of 25HC in the membrane as well as the interactions it might have with lipids. We have studied two complex model membrane systems, one similar to the late endosome membrane and the other one to the plasma membrane. Our results reinforce that 25HC is inserted in the membrane in a relative stable location similar to but not identical to cholesterol. 25HC fluctuates in the membrane to a much greater degree than cholesterol, but the effect of 25HC on the phospholipid order parameters is not significantly different. One of the most notable facts about 25HC is that, unlike cholesterol, this molecule tends to aggregate, forming dimers, trimers and higher-order aggregates. These aggregates are formed spontaneously through the formation of hydrogen bonds between the two 25HC atoms, the formation of hydrogen bonds being independent of the studied system. Remarkably, no contacts or hydrogen bonds are observed between 25HC and cholesterol molecules, as well as between cholesterol molecules themselves at any time. It would be conceivable that 25HC, by forming high order aggregates without significantly altering the membrane properties, would modify the way proteins interact with the membrane and henceforth form a true innate antiviral molecule.

25-羟基胆固醇（25HC）是最重要的氧固醇分子之一，可被细胞用于抵抗细菌和病毒感染，但定义其生物学作用的机制尚不清楚。利用分子动力学，我们旨在描述膜中25HC的取向和位置，以及它与脂质的相互作用。我们研究了两种复杂的模型膜系统，一种类似于晚期内体膜，另一种类似于质膜。我们的结果加强了将25HC插入膜的相对稳定位置，该位置类似于但不等同于胆固醇。25HC在膜中的波动程度要比胆固醇大得多，但25HC对磷脂有序参数的影响没有显着差异。关于25HC的最显着事实之一是，与胆固醇不同，该分子倾向于聚集，形成二聚体，三聚体和更高阶的聚集体。这些聚集体是通过两个25HC原子之间氢键的形成而自发形成的，氢键的形成与所研究的系统无关。值得注意的是，在任何时候，25HC和胆固醇分子之间以及胆固醇分子本身之间都没有观察到接触或氢键。可以想象，25HC通过形成高阶聚集体而不会显着改变膜的性质，将改变蛋白质与膜相互作用的方式，从而形成真正的先天抗病毒分子。这些聚集体是通过两个25HC原子之间氢键的形成而自发形成的，氢键的形成与所研究的系统无关。值得注意的是，在任何时候，25HC和胆固醇分子之间以及胆固醇分子本身之间都没有观察到接触或氢键。可以想象，25HC通过形成高阶聚集体而不会显着改变膜的性质，将改变蛋白质与膜相互作用的方式，从而形成真正的先天抗病毒分子。这些聚集体是通过两个25HC原子之间氢键的形成而自发形成的，氢键的形成与所研究的系统无关。值得注意的是，在任何时候，25HC和胆固醇分子之间以及胆固醇分子本身之间都没有观察到接触或氢键。可以想象，25HC通过形成高阶聚集体而不会显着改变膜的性质，将改变蛋白质与膜相互作用的方式，从而形成真正的先天抗病毒分子。