DESPOT adds directionality to knowledge-based protein–ligand scoring
- Knowledge-based potentials are interpretable scoring functions, but most treat space around protein atoms as isotropic.
- DESPOT is an all-atom anisotropic potential that assigns atoms to isotropic, axially symmetric or fully anisotropic classes by hybridization and bonding.
- It uses a positionally averaged reference state and a 'void' ligand atom type so regions preferentially left empty can be represented.
- The authors position it as a direction-aware successor to existing knowledge-based scoring.
💡 Points
Directionality is exactly what hydrogen bonds, halogen bonds and pi contacts need and what isotropic potentials blur, so this targets a real weakness in how I triage docked poses. The void atom type is a neat touch for pocket regions that ligands avoid. What I will check before trusting it: performance on my own targets and decoy sets, not just benchmarks, and whether it ranks congeneric series rather than only separating actives from decoys.
DESPOT: Direction-Enhanced Scoring POTentials for Scoring of Protein–Ligand Interactions ↗