Tyagi Chetna, Marik Tamás, Szekeres András, Vágvölgyi Csaba, Kredics László, Ötvös Ferenc
Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
Institute of Biochemistry, Biological Research Centre, Temesvári krt. 62, H-6726 Szeged, Hungary.
Life (Basel). 2023 Nov 30;13(12):2288. doi: 10.3390/life13122288.
We previously reported on a novel peptaibol, named Tripleurin XIIc (TPN), an 18-residue long sequence produced by the fungus . We elucidated its 3D structure via classical and accelerated molecular dynamics simulation (aMD) methods and reported the folding dynamics of TPN in water and chloroform solvents. Peptaibols, in general, are insoluble in water, as they are amphipathic and may prefer hydrophobic environments like transmembrane regions. In this study, we attempted to use aMD simulations to model an all-atom bacterial membrane system while placing a TPN molecule in its vicinity. The results highlighted that TPN was able to introduce some disorder into the membrane and caused lipid clustering. It could also enter the transmembrane region from the water-bilayer interface. The structural dynamics of TPN in the transmembrane region revealed a single energetically stable conformation similar to the one obtained from water and chloroform solvent simulations reported by us previously. However, this linear structure was found to be at the local energy minimum (stable) in water but at a metastable intermediate state (higher energy) in chloroform. Therefore, it could be said that the water solvent can be successfully used for folding simulations of peptaibols.
我们之前报道过一种名为三联菌素XIIc（TPN）的新型肽菌素，它是由真菌产生的一个18个残基的长序列。我们通过经典和加速分子动力学模拟（aMD）方法阐明了其三维结构，并报道了TPN在水和氯仿溶剂中的折叠动力学。一般来说，肽菌素不溶于水，因为它们具有两亲性，可能更喜欢跨膜区域等疏水环境。在本研究中，我们尝试使用aMD模拟来构建一个全原子细菌膜系统模型，同时将一个TPN分子置于其附近。结果表明，TPN能够在膜中引入一些无序状态并导致脂质聚集。它还可以从水 - 双层界面进入跨膜区域。TPN在跨膜区域的结构动力学揭示了一种能量稳定的单一构象，类似于我们之前报道的在水和氯仿溶剂模拟中获得的构象。然而，这种线性结构在水中处于局部能量最小值（稳定），而在氯仿中处于亚稳态中间状态（能量更高）。因此，可以说水溶剂可成功用于肽菌素的折叠模拟。
