High-confidence placement of low-occupancy fragments into electron density using the anomalous signal of sulfur and halogen atoms.

ABSTRACT: Fragment-based drug design using X-ray crystallography is a powerful technique to enable the development of new lead compounds, or probe molecules, against biological targets. This study addresses the need to determine fragment binding orientations for low-occupancy fragments with incomplete electron density, an essential step before further development of the molecule. Halogen atoms play multiple roles in drug discovery due to their unique combination of electronegativity, steric effects and hydrophobic properties. Fragments incorporating halogen atoms serve as promising starting points in hit-to-lead development as they often establish halogen bonds with target proteins, potentially enhancing binding affinity and selectivity, as well as counteracting drug resistance. Here, the aim was to

SUBMITTER: Ma S 

PROVIDER: S-EPMC11154595 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature