Contact: Dr. Chia-Lung Hsieh 謝佳龍博士

 

Biological membrane consist of a chemical diverse set of lipids and they have been shown to play multiple cellular roles including defence, intracellular transport, signal transduction and membrane fusion. In prokaryotic cell, the development of bacterial resistance to current available antibiotics is a major problem for healthcare worldwide. The rational development of new therapeutics relies upon a detailed knowledge of how drugs and potential drugs interact with the membranes that surround and protect bacteria. In eukaryotic cell, the pathological changes in lipid environment has been associated with development of diseases such as Alzheimer’s, Parkinson’s, diabetes, anxiety, depression and more. With increasing computational power, molecular dynamics (MD) have become a well-developed tool that can be utilised to explore the time-dependent behaviour of biological molecules, from single molecules to more complex multi- component systems. To this end, I have employed coarse- grained molecular dynamics simulations for a broad range of studies in biological system from Gram-negative bacterial membrane to mammalian neuronal membrane models.

 

For the bacterial membrane studies, I develop different models of lipopolysaccharide (LPS) lipid, a molecule found in the outer leaflet of the outer membrane of Gram-negative bacteria. With the LPS model, I explore the interaction of pristine carbon fullerenes (C60) with E. coli membranes and predict that pristine C60 has a limited tendency to penetrate LPS leaflet in the presence  of  calcium  ions  at  310  K,  but  more  readily  penetrate  the  leaflet  at  higher temperature and in the presence of sodium ions or when small patches of POPE lipids are present within the LPS membranes. Furthermore, I also use these LPS models for simulations that are designed to understand more general principles of molecular interaction between native membrane protein and lipids in an E. coli cell envelope. The results revealed that both the outer and inner membranes curve in a manner dependent on the size of the membrane proteins.  For  the  neuronal  plasma  membrane  studies,  we  use  the  advance  of  recent computational power and the MARTINI lipid force fields to simplify and test a realistically “less” complex neuronal plasma membrane model from previous work on an idealised complex mammalian neuronal membrane. Moreover, with this “less” complex neuronal membrane model developed, we are able to study with amyloid peptides to investigate the protein-lipid interplay at atomistic resolution.