ABCG2, which is a crucial protein in development of multidrug resistance in cancer cells, is a transporter machine, acting like a vacuum cleaner in the membrane that removes a wide range of drugs from the cell. Given its heavily fatty environment, it's not surprising that its function is highly influenced by lipids and cholesterol. To shed light on the underlying mechanism, cryo-EM and functional assays in the Locher lab at ETH Zürich, were combined with computational microscopy using NAMD and VMD at the Center, to discover, for the first time, that lipids can enter the protein's binding pocket and directly interact with the bound drugs. More interestingly, cholesterol is found to guard the binding pocket's gates from other lipids, thus accelerating the transport function of the protein. Read more about the study in a recent PNAS paper.
The Future of Biomolecular Modeling
A 2015 TCBG Symposium brought together scientists from across the Midwest to brainstorm about what's on the horizon for computational modeling. See a summary of what these experts foresee.
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A Look Ahead
The Urbana NIH Center previews what it will propose for the 2017-2022 funding cycle. By Lisa Pollack.
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Announcements
Auburn WorkshopTargeting Lipid-protein interactions to fight cancerGoing After LipidsMultiple VMD/NAMD research programmer positions available
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Remembering Klaus Schulten
Recent Publications All Publications
- Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants. Proc. Natl. Acad. Sci. USA, 2023.
- End-to-end AI framework for interpretable prediction of molecular and crystal properties. Machine Learning: Science and Technology, 2023.
- Insights into substrate transport and water permeation in the mycobacterial transporter MmpL3. Biophys. J., 2023.
- Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells. Nat. Commun., 14:59. 2023.
- Cryo-EM structures of human ABCA7 provide insights into its phospholipid translocation mechanisms. EMBO Journal, 42:e111065. 2022.
- Backbone amides are key determinants of Cl- selectivity in CLC ion channels. Nat. Commun., 13:7508. 2022.
- Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification. Nat. Commun., 13:6877. 2022.
- Structures of the TMC-1 complex illuminate mechanosensory transduction. Nature, 610:796-803. 2022.
- Targeting lipid-protein interaction for drug development: Development of a novel resistance-proof Syk inhibitor for acute myeloid leukemia. Nat. Chem. Biol., 2022.
- Proton-driven alternating access in a spinster lipid transporter. Nature Communications, 13:5161. 2022.
Highly Cited
Protein domain movements: Detection of rigid domains and visualization of hinges in comparisons of atomic coordinates. PROTEINS: Structure, Function, & Genetics, 29:1-14, 1997.
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