Molecular Simulation × AI Reveals Structural Changes of Transporter Proteins

Transporter proteins exist in the plasma membrane and transport various substrates into and out of the cell. It is believed that substrates are transported by a mechanism involving conformational changes called alternating access. Therefore, it is necessary to elucidate the structural changes in order to understand the mechanism. We have elucidated the conformational changes of the oxalate transporter, which transports oxalic acid, a substance contained in vegetables and nuts that causes urinary tract stones, by combining molecular dynamics (MD) simulations and the structure prediction AI AlphaFold. MD simulations predicted the inward-open conformation, which is experimentally difficult to analyze, and AlphaFold successfully predicted mutations that stabilize the inward-open conformation.

Accelerated Molecular Dynamics and AlphaFold Uncover a Missing Conformational State of Transporter Protein OxlT
J. Ohnuki, T. Jaunet-Lahary, A. Yamashita, and K. Okazaki, J. Phys. Chem. Lett. 15, 725–732 (2024).