Computational Biology Division, DRDO BU CLS, Coimbatore, India.
Periyar University, Salem, India.
J Biomol Struct Dyn. 2020 Jan;38(1):186-199. doi: 10.1080/07391102.2019.1570341. Epub 2019 Feb 10.
The structural stability and transport properties of the cyclic peptide nanotube (CPN) 8 × [Cys-Gly-Met-Gly] in different phospholipid bilayers such as POPA (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acid), POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol) and POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine) with water have been investigated using molecular dynamics (MD) simulation. The hydrogen bonds and non-bonded interaction energies were calculated to study the stability in different bilayers. One µs MD simulation in POPA lipid membrane reveals the stability of the cyclic peptide nanotube, and the simulations at various temperatures manifest the higher stability of 8 × [Cys-Gly-Met-Gly]. We demonstrated that the presence of sulphur-containing amino acids in CPN enhances the stability through disulphide bonds between the adjacent rings. Further, the water permeation coefficient of the CPN is calculated and compared with human aquaporin-2 (AQP2) channel protein. It is found that the coefficients are highly comparable to the AQP2 channel though the mechanism of water transport is not similar to AQP 2; the flow of water in the CPN is taking place as a two-line 1-2-1-2 file fashion. In addition to that, the transport behavior of Na and K ions, single water molecule, urea and anti-cancer drug fluorouracil were investigated using pulling simulation and potential of mean force calculation. The above transport behavior shows that Na is trapped in CPN for a longer time than other molecules. Also, the interactions of the ions and molecules in Cα and mid-Cα plane were studied to understand the transport behavior of the CPN. AbbreviationsAQP2Aquaporin-2CPNCyclic peptide nanotubeMDMolecular dynamicsPOPA1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acidPOPE1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolaminePOPG1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerolPOPS1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserineCommunicated by Ramaswamy H. Sarma.
已使用分子动力学 (MD) 模拟研究了环肽纳米管 (CPN) 8×[Cys-Gly-Met-Gly]在不同磷脂双层（如 POPA（1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸）、POPE（1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸乙醇胺）、POPC（1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱）、POPG（1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸甘油）和 POPS（1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸丝氨酸）与水的结构稳定性和传输特性。计算氢键和非键相互作用能以研究不同双层中的稳定性。在 POPA 脂质膜中进行的 1µs MD 模拟表明了环肽纳米管的稳定性，而在不同温度下的模拟则表明 8×[Cys-Gly-Met-Gly]的稳定性更高。我们证明了 CPN 中含硫氨基酸通过相邻环之间的二硫键增强了稳定性。此外，还计算并比较了 CPN 的水渗透系数与人类水通道蛋白-2（AQP2）通道蛋白。尽管水在 CPN 中的运输机制与 AQP2 不同，但发现系数与 AQP2 通道非常相似；CPN 中的水流是以两行 1-2-1-2 文件的形式进行的。除此之外，还通过牵引模拟和平均力势计算研究了 Na 和 K 离子、单个水分子、尿素和抗癌药物氟尿嘧啶的传输行为。上述传输行为表明，与其他分子相比，Na 被困在 CPN 中的时间更长。此外，还研究了 Cα 和中 Cα 平面内离子和分子的相互作用，以了解 CPN 的传输行为。缩写词 AQP2水通道蛋白 CPN 环肽纳米管 MD 分子动力学 POPA 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸 POPE 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸乙醇胺 POPG 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸甘油 POPS 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸丝氨酸 由 Ramaswamy H. Sarma 传达。
