Fragmenstein: predicting protein-ligand structures of compounds derived from known crystallographic fragment hits using a strict conserved-binding-based methodology.

ABSTRACT: Current strategies centred on either merging or linking initial hits from fragment-based drug design (FBDD) crystallographic screens generally do not fully leaverage 3D structural information. We show that an algorithmic approach (Fragmenstein) that 'stitches' the ligand atoms from this structural information together can provide more accurate and reliable predictions for protein-ligand complex conformation than general methods such as pharmacophore-constrained docking. This approach works under the assumption of conserved binding: when a larger molecule is designed containing the initial fragment hit, the common substructure between the two will adopt the same binding mode. Fragmenstein either takes the atomic coordinates of ligands from a experimental fragment screen and combines the ato

SUBMITTER: Ferla MP 

PROVIDER: S-EPMC11731148 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature