A Computational Study of Cation-Phospholipid Interactions and Transition-State Formation in Membrane

Project Details


Background: Biomembranes are very complex heterogeneous systems mainly consisting of many different types of lipids. Biological membranes play significant roles in controlling the partition, transportation, and communication functions of the physiological states of cells. Membranes can fuse with each other to form large membrane under particular conditions. Membrane fusion plays a significant biological role in, for example, intracellular trafficking, recycling, viral inflecting, and neurotransmitter release. Its medical applications include drug delivery and gene therapy.Motivations: Although many efforts have been given to study the mechanism of membrane fusion and the self-assembly of lipids into a bilayer or a vesicle, however, the underlying molecular mechanisms remain poorly understood. Our recent study shows the unusual fast rotation of the dihedral angle adjacent to the double bond of lipids may play critical roles in membrane fusion and re-organization. Moreover, Ca2+ cations strongly bind to the phospholipid bilayers and are capable to induce membrane fusion. In contrast, the divalent Mg2+ cations have relatively limited effect. Thus, it is important to investigate these processes at the molecular basis using various levels of computational methods.Methodology: Quantum chemical calculation, constant-temperature molecular dynamics, an effective phase space sampling algorithm, replica-exchange molecular dynamics simulations , and structural analysis will be employed in this study.Objectives: Specific objectives include (1) Unraveling the factors that determine the distinct binding affinities of Ca2+-phospholipid and Mg2+-phospholipid complexes, (2). investigation and understanding of the formation of the transition-state (pre-stalk state) in membrane fusion, and (3). delineating and analysis of the molecular mechanism of the spontaneous lipid aggregation into a bilayer or a vesicle. Knowledge of the above objectives of lipid membranes is essential for our general understanding of biomembrane functioning.Broader Impact: This project will serve as an interface for integrating research and education. The computational and bioinformatics methods used and developed in this project will be incorporated into the graduate-level courses. The computational infrastructure and biomolecular simulations in the chemistry department at National Central University are expected to be significantly improved. The wider impact of this project includes the training of interdisciplinary graduate students for studying membrane problems. Understanding the biophysical mechanisms of membrane fusion has implications for pharmacology, engineering, and nanoscience.
Effective start/end date1/08/1631/07/17

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 12 - Responsible Consumption and Production
  • SDG 14 - Life Below Water
  • SDG 17 - Partnerships for the Goals


  • Cation-Lipid Interaction
  • Dihedral Angle Rotation
  • Membrane Fusion
  • Lipid Self-Assembly
  • Free Energy Landscape


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