Protein Dynamics at the Interface of AI and Experimental Structural Biology
Training and Research
The Mchaourab lab has undergone multiple personality makeovers. Our roots are in experimental sciences but our branches are reaching for the horizon of Artificial Intelligence. We are fascinated by how proteins carry out function. Function requirements changes in the shape of proteins, their three dimensional structures. Proteins have parts that twist, bend, gate leading to a spectrum of conformations. Decoding how nature evolved principles of protein conformational dynamics is a key question in the laboratory. We believe the recent revolution in AI methods for proteins set the stage to answer these questions.
Our targets are membrane transporters that are translationally important. For example, we work on mammalian multidrug transporters such as ABCB1 also know as P-glycoprotein (Pgp). Pgp is the master regulator of xenobiotic transport in humans. Its expression has been associated with resistance to chemotherapy.
We have published work showing how this molecular machine transports its substrate and how clinical inhibitors stop it in its tracks. Another example is human serotonin transporter (SERT). SERT is the target of antidepressants and the site of action of drugs of abuse. SERT N-terminal hub is the site of phosphorylation and interactions with signaling protein allowing control of function.
Rotation projects
1) How lipids shape the dynamics of transporters (experimental and computational)
2) Building protein databases for AI training (Computational)
3) Design and Screening of molecules to stabilize serotonin transporter (experimental and computational)
4) In silico screening of small molecules for P-glycoprotein