The Nature of Nanodisc Lipids Influences Fragment-Based Drug Discovery Results.

ABSTRACT: Membrane proteins (MPs) are important yet challenging targets for drug discovery. MPs can be reconstituted in protein-lipid Nanodiscs (NDs), which resemble the native membrane environment. Drug-membrane interactions can affect the apparent binding stoichiometry and affinity, as well as the kinetics of ligands for a particular target, which is important for the extrapolation to pharmacokinetic studies. To investigate the role of the membrane, we have applied fragment-based drug discovery (FBDD) methods to cytochrome P450 3A4 (CYP3A4), reconstituted in NDs composed of different phosphocholine lipids: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), or 1,2-diphytanoyl-sn-glycero-3-phosphocholine

SUBMITTER: Knetsch TGJ 

PROVIDER: S-EPMC11909325 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature