Accelerating Cryptic Pocket Discovery Using AlphaFold.

ABSTRACT: Cryptic pockets, or pockets absent in ligand-free, experimentally determined structures, hold great potential as drug targets. However, cryptic pocket openings are often beyond the reach of conventional biomolecular simulations because certain cryptic pocket openings involve slow motions. Here, we investigate whether AlphaFold can be used to accelerate cryptic pocket discovery either by generating structures with open pockets directly or generating structures with partially open pockets that can be used as starting points for simulations. We use AlphaFold to generate ensembles for 10 known cryptic pocket examples, including five that were deposited after AlphaFold's training data were extracted from the PDB. We find that in 6 out of 10 cases AlphaFold samples the open state. For plasmepsin

SUBMITTER: Meller A 

PROVIDER: S-EPMC10373493 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature