1. Bio-mimetic Membrane Systems
離子對雙親分子(ion pair amphilphile,IPA),是將陽離子型及陰離子型界面活性劑混合,並去除對離子後製備而成,其分子結構和生物磷脂相似,有機會取代現行成本較昂貴的微脂粒(liposome),作為新一代的藥物釋放或基因療法(gene therapy)之載體。本研究以適當的力場模型(force field)搭配數值方法,計算由IPA所形成之雙層膜(bilayer)其構造、力學性質與熱力學性質,提供實驗上製備陰陽離子液胞(catanionic vesicle)所需資訊。
Phosphatidylcholine (PC) is one of the most common phospholipids and the major component of the cell membrane bilayer. Wrapping PC bilayers into hollow spherical structures results in PC vesicles, also named liposomes, which have great potentials in pharmaceutical applications. Yet the actual application of liposome is limited due to the high cost of PC. Ion pair amphiphile (IPA) is a complex composed of a pair of cationic and anionic surfactants after removing their residual counter-ions, resulting in a PC-like molecular structure. Therefore, IPA has been considered as one of the cheaper PC substitutes. In this project, we applied molecular dynamics simulations to characterize IPA bilayer properties from three different aspects: (1) examining the effects of alkyl chain lengths, (2) identifying the importance of cationic and anionic components of IPA via asymmetric chain length combinations, and (3) characterizing the effects of cholesterol additive on IPA bilayers. Simulations results showed that cationic components have greater effects on IPA bilayers in terms of both the membrane structure and the membrane elasticity. The anionic surfactants, in contrast, play more important role in the presence of cholesterol additive due the H-bonds between the their hydrophilic groups. The presented results provide valuable molecular insights into the IPA bilayer systems, which can serve as useful reference for fabricating IPA vesicles and future application designs.
self-assembly process of IPA vesicles
Fusion free energy analysis of two IPA bilayers
2. Protein Folding
運用『分子動態模擬』與『搭配進階取樣(advanced sampling)』,探討蛋白質摺疊機制,並應用于生醫領域,如蛋白質於介面折疊行為,以及類澱粉蛋白纖維化與沈澱。由模擬的結果搭配實驗和理論,已成功得出類澱粉蛋白hIAPP的聚集沉澱機制。此外,我們發展簡易熱力學模型,用以預測蛋白質於氣液界面之結構趨勢。
The fibril deposits of amyloid proteins are implicated in more than 20 human diseases, including Alzheimer’s disease, Parkinson’s disease, and type II diabetes. Yet the aggregation mechanism of amyloid fibrils remains illusive. Specifically, the amyloid fibrils of human islet amyloid polypeptide (hIAPP), or human amylin, are closely related to the development of type II diabetes. In this work, we utilized atomistic molecular dynamics combined with advanced sampling techniques to study the conformations of hIAPP monomers, oligomers, and mature fibrils and the corresponding conformational free energies. We compared the simulation data with experimental data to study the molecular mechanism of hIAPP fibril formation. We identified the aggregation mechanism of hIAPP and characterized the important intermediate species during the fibrillization process, which provides valuable insights into the future inhibitor designs. We also revealed new pathological roles of hIAPP where the aggregation of hIAPP triggers the deposition of nonamyloidogenic peptide.
Dimerization free energy landscape of hIAPP.
[Buchanan, L. E.; Dunkelberger, E. B.; Tran, H. Q.; Cheng, P.-N.; Chiu, C.-C.; Cao, P.; Raleigh, D. P.; de Pablo, J. J.; Nowick, J. S.; Zanni, M. T. Mechanism of IAPP Amyloid Fibril Formation Involves an Intermediate with a Transient Β-Sheet. Proceedings of the National Academy of Sciences 2013, 110 (48), 19285–19290.]
Fast estimation of protein conformational free energy change at air/water interface
3. Polymer for Li-ion Battery
鋰離子電池系統是由正負電極,電解液,以及隔離膜等組成。我們利用分子動力學模擬,探討由聚醚以及含氟鏈段組成的新型兩性共聚高分子黏著劑,在正極以及電解質界面對鋰離子傳遞的影響。此外我們也針對高分子在電極表面的鋰離子遷入遷出之影響進行分析。
We utilized molecular dynamics (MD) simulations to explore the effects of novel copolymer binder at the cathode/electrolytes interface. The radial distribution function and Li+ coordination analyses showed the interaction between Li+ and PF6- is reduced on the binder surface. The coordination around Li+ have gradually changed from EC and DEC solvent to polymer EO-segments as Li+ approaching the binder surface. Yet, the overall diffusivity of the surface bound Li+ is reduced as the surface EO-chain density increases. The combined results conclude that the addition of the EO chains can reduce the interaction between Li+ and PF6- but decrease the overall Li+ diffusivity on the binder surface. The two competing effects provide microscopic insights into the future designs of functional polymer binder.
Simulation of Lithium intercalation and deintercaltion at electrode interface
Coordination ratio, total coordination number, and density profiles of polymer/electrolyte systems.
7. 2019/08 - 2021/07 仿生陰陽離子液胞的膜通透與膜融合特性之基礎熱力學研究
6. 2018/08 - 2019/07 快速預測蛋白質於氣液界面的結構穩定性
5. 2017/10 - 2019/09 臺德(DE)國合計畫-高安全性及高效能之前瞻全固態電池的概念評估和開發(協同主持人)
4. 2017/01 - 2018/12 奈米國家型科技計畫-高傳導度鋰離子電池固態電解質之合成關鍵技術開發 (共同主持人)
3. 2017/08 - 2018/07 以分子模擬探討類乙醇體陰陽離子液胞之結構、機械、與通透特性
2. 2015/08 - 2017/07 利用分子模擬探討陰陽離子對雙親分子形成之仿生膜特性
1. 2014/03 - 2015/07 運用分子模擬解析陰陽離子界面活性劑之自組裝特性