Memorization Bias Impacts Modeling of Alternative Conformational States of Symmetric Solute Carrier Membrane Proteins with Methods from Deep Learning.

ABSTRACT: Conformational memorization impacts the performance of AlphaFold in modeling the dynamic structures of proteins. The Solute Carrier (SLC) superfamily of integral membrane proteins transport a wide array of small molecules across plasma and organelle membranes, and function as important drug transporters and as viral receptors. They populate different conformational states during the solute transport process, including outward-open, intermediate (occluded), and inward-open conformational states. For some SLC proteins this structural "flipping" corresponds to swapping between conformations of their N-terminal and C-terminal symmetry-related sub-structures. Conventional AlphaFold2, AlphaFold3, or Evolutionary Scale Modeling methods typically generate models for only one of these multiple conf

SUBMITTER: Swapna GVT 

PROVIDER: S-EPMC11275918 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature