... understanding life in molecular detail

Dr Antreas Kalli

Molecular dynamics simulations, Membrane proteins,Lipid membranes, Molecular modelling

Molecular simulations can provide a ‘computational microscope’ enabling us to study membrane proteins at the molecular level. Our group uses multi-scale molecular dynamics simulations (i.e. coarse-grained and all-atom) and molecular modelling to provide molecular/structural and dynamic details about membrane proteins and membranes.

Current major projects include:
  • Cell signalling receptors and related proteins
  • Membrane transport proteins
  • High-throughput computational approaches
  • Complex model membranes

We use multi-scale molecular dynamics simulations to study how membranes and membrane proteins function. Multi-scale simulations enable us to represent the system in different resolutions (i.e. coarse-grained and all-atom) depending on the time and length scale of interest. Coarse-grained simulations enable us to study longer-scale phenomena e.g. protein/lipid interactions. All-atom simulations allow us to study conformational changes within proteins and to refine protein/lipid and protein/protein complexes.

We use molecular dynamics simulations to study proteins in the following areas:

  1. Immune response: Our studies are mainly focused on the T-cell receptor. The T-cell receptor is a multisubunit transmembrane protein located in T-lymphocytes. It is critical for the survival and function of T-cells and for the immune response, as it initiates various biological processes responsible for the protection of the organism from infectious agents. We use our computational methodologies to understand the T-cell receptor activation mechanism and how this is regulated by cytosolic kinases and its lipid environment.
  2. Cell surface receptors that are involved in transmission of signals across cell membranes e.g. integrins and related proteins. Integrins play a key role in many biological functions, ranging from immune responses to cancer. We aim to understand how the integrin receptor is activated by talin and kindlins.
  3. Membrane proteins that transport molecules and/or ions across cell membranes. Our studies focus on two proteins: i) Band 3 and ii) Piezo1. Both are very important in health and disease and thus malfunction of these proteins results in human diseases such as anemias and other cardiovascular diseases. With our studies, we aim to understand how these proteins behave in cell membranes and how this helps their ability to transport molecules/ions in and out of cells. A key aspect of our research is to simulate these protein in model membranes that resemble the native membranes that such proteins function.
  4. How we can develop high-throughput computational approaches that allows us to study proteins faster and more efficiently. So far, we have developed a high-throughput approach that allows us to study how peripheral membrane proteins bind to cell membranes. This approach enables us to understand how large sets of lipid binding domains of the same family of proteins – as opposed to individual domains - attach to cell membranes.
Detailed research programme                  Close ▲

University Academic Fellow
Dphil (Oxford) Postdoc (Oxford) 2012-2016

6.30 LIGHT Labs, Medicine
School of Molecular and Cellular Biology
0113 343 7722


Selected Publications

  1. Kalli, A. C.; Reithmeier, R. A. F. (2018) Interaction of the Human Erythrocyte Band 3 Anion Exchanger 1 (AE1, SLC4A1) with Lipids and Glycophorin A: Molecular Organization of the Wright (Wr) Blood Group Antigen. PLoS Comput. Biol. 14 (7), e1006284.

  2. Yamamoto E, Kalli AC, Yasuoka L, Sansom SMP (2016) Interactions of pleckstrin homology domains with membranes: Adding the bilayer back via high throughput molecular dynamics. Structure 24(8):1421-1431

  3. Kalli AC, Sansom MSP, Reithmeier RAF (2015) Molecular dynamics simulations of the bacterial UraA H+-Uracil symporter in lipid bilayers reveal a closed state and a selective interaction with cardiolipin. PLoS Comput Biol 11: e1004123.

  4. Naughton FB, Kalli AC, Sansom MSP (2016) Association of peripheral membrane proteins with membranes: Free energy of binding of GRP1 PH domain with phosphatidylinositol phosphate-containing model bilayers. J Phys Chem Lett. 2016:1219-24