Evaluation of Small-Molecule Binding Site Prediction Methods on Membrane-Embedded Protein Interfaces.

ABSTRACT: Increasing structural and biophysical evidence suggests that many drug molecules bind to the protein-membrane interface region in membrane protein structures. An important starting point for drug discovery is the determination of a ligand's binding site; however, this information is missing for many membrane proteins, especially for their membrane-embedded parts. Therefore, we tested the performance of computational methods for ligand binding site prediction in the protein intramembrane region. We compiled data sets containing GPCR- and ion channel-ligand complexes and compared method performance relative to a soluble protein data set obtained from PDBBind. We tested state-of-the-art geometry-based (Fpocket, ConCavity), energy probe-based (FTSite), machine learning-based (P2Rank, GRaSP), a

SUBMITTER: Pliushcheuskaya P 

PROVIDER: S-EPMC12264969 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature