#23 · Structural bio & protein design

Explicit conformational pathways in membrane proteins from simulation and cryo-EM

The common thread is treating conformational change as an explicit pathway rather than a static end state. Atomistic MD of intact and ND4/ND5-truncated complex I captures a ND2 P-side conformational change, which occurs more readily in the truncated model. For the human voltage-gated proton channel hHV1, the activation pathway is resolved by integrating constant-pH MD, weighted-ensemble sampling, and AlphaFold modeling. A cryo-EM study combines iterative 3D classification, simulated-particle error quantification, and global thermodynamic modeling to extract minute energy differences among heterogeneous complexes. What is new is pairing enhanced sampling and thermodynamic readouts with pathway-level interpretation for membrane proteins. A carbohydrate survey, which uses Cremer-Pople puckering coordinates to compare chair and non-chair pyranose conformations, adds a caution: distortions in PDB data may reflect experimental conditions rather than biology.