Reaction-aware covalent docking & scoring
BCover ranks covalent ligands by asking the question that matters in covalent drug design: does the compound fit the pocket and adopt a chemically meaningful pre-reactive pose that supports the intended mechanism?
A two-step pipeline pairs constrained pre-reactive docking with quantum-chemistry-informed scoring — Fukui-function reactivity, LM5 entropy, QM transition-state geometry — so rankings carry mechanistic context, not just shape complementarity.
Reported on 4HCU / ITK from the Covalid benchmark — strong discrimination between covalent binders and decoys.
30× enrichment in the top 1% of the ranked library — the regime where triage decisions actually get made.
Per ligand on AWS GPU — fast enough to screen large covalent libraries before synthesis or biochemical follow-up.
Constrained docking, transition-state physics, reactivity-aware ranking — packaged for covalent programs.
Two-step covalent docking
Pre-reactive constrained docking followed by reaction-aware scoring — separating where the ligand sits from whether it can actually react.
Reactive residue & warhead detection
Automated identification of nucleophilic residues in the pocket and electrophilic warheads in the ligand, with no manual annotation required.
Constrained pre-reactive poses
BDocker simulated annealing with a modified MMFF94 force field imposes physically motivated residue–warhead orientation constraints.
QM transition-state geometry
Reaction geometry informed by high-quality quantum-chemistry transition-state data for major covalent-binding reaction classes.
Fukui + LM5 entropy scoring
Scoring blends XTB/DFT-supported quantum chemistry, Fukui-function reactivity terms, QM-derived molecular potentials and LM5 entropy.
Cloud-native GPU deployment
Deployable on AWS with GPU support for scalable screening — fully automated from pocket detection through ranked candidate list.
How a BCover screening run reaches its ranked list.
- 01Pocket detection around the target site
- 02Reactive residue detection in the pocket
- 03Automated simulation box setup
- 04Ligand warhead detection
- 05Constrained pre-reactive docking (BDocker SA + modified MMFF94)
- 06Pocket interaction profiling of the pre-reactive state
- 07Pose scoring & ligand ranking with QM + LM5 entropy