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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TCBG and the National Strategic Computing Initiative
Now that the U.S. has a clear directive to build an exascale computer, Klaus Schulten weighs in on what this could mean for the field of computational biophysics.
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Targeting Lipid-protein interactions to fight cancerGoing After LipidsMultiple VMD/NAMD research programmer positions availableUI News:Spike Protein Flexibility Enhanced by Post-translational Modifications in Human Cells
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Remembering Klaus Schulten
Recent Publications All Publications
- 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.
- Proton-driven alternating access in a spinster transporter, an emerging family of broad-specificity efflux pumps. Nat. Commun., 13:5161. 2022.
- Intelligent resolution: Integrating Cryo-EM with AI-driven multi-resolution simulations to observe the severe acute respiratory syndrome coronavirus-2 replication-transcription machinery in action. The International Journal of High Performance Computing Applications. 2022.
- Molecular View into Preferential Binding of the Factor VII Gla Domain to Phosphatidic Acid. Biochemistry, 61:1694-1703. 2022.
- py-MCMD: Python Software for Performing Hybrid Monte Carlo/Molecular Dynamics Simulations with GOMC and NAMD. J. Chem. Theory Comput. 2022.
- Phthalate monoesters act through peroxisome proliferator-activated receptors in the mouse ovary. Reproductive Toxicology, 110:113-123. 2022.
