Protein Dynamics at the Interface of AI and Experimental Structural Biology
Proteins carry out their functions by cycling among conformations, and the free energy differences among those conformations determine how a transporter behaves in the cell. We define the conformational ensembles of membrane transporters with double electron-electron resonance (DEER) spectroscopy, cryo-electron microscopy and molecular dynamics simulations, and we develop deep learning methods that predict them. Our targets include P-glycoprotein (Pgp, also known as ABCB1), which has a central role in the clearance of xenobiotics in humans and is associated with resistance to chemotherapy, and the human serotonin transporter (SERT), a target of antidepressants.
The AI components of this work are carried out within the Center for AI in Protein Dynamics at Vanderbilt University. Read about our research.
New paper: Drug-bound outward-facing conformation of a heterodimeric ABC exporter suggests a putative mechanism of drug translocation, Tang et al., Nature Communications, 2025.
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Rotation projects
- How lipids shape the dynamics of transporters (experimental and computational)
- Building protein databases for AI training (computational)
- Design and screening of molecules to stabilize the serotonin transporter (experimental and computational)
- In silico screening of small molecules for P-glycoprotein