# Bromodomains¶

## BRD4 Bromodomain¶

In this tutorial we redock the ligand from crystal structure with PDB code 4PCI. This is a 7-μM ligand of the N-terminal bromodomain of BRD4, abbreviated as BRD4(1) [Zhao2014]. We also try to dock an enantiomer of the original ligand.

In order to run this test case execute the following commands:

cd test_cases/bromodomains/BRD4
../../../bin/seed_4 seed.inp >& log


The two enantiomers are docked by SEED which identifies the correct pose for the enantiomer observed in the crystal structure (white molecule) while the other enantiomer does not fit into the binding pocket and it is docked on the rim of the binding site. The correct enantiomer forms a hydrogen bond with the conserved asparagine of BRD4(1) (grey residue) replacing the role of the acetylated lysine from the histone tail.

Note also the gap in energy between the top pose of the correct enantiomer and all other poses.

Name Tot ElinW rec_des frg_des vdW DElec DG_hydr
4pci_ligand -25.97 -9.58 5.16 4.31 -25.86 -5.34 -4.24
4pci_ligand -20.67 -6.14 5.21 4.45 -24.19 -1.90 -4.24
4pci_ligand -19.62 -4.77 5.21 4.34 -24.41 -0.53 -4.24
4pci_ligand -19.43 -5.42 5.66 4.32 -24.00 -1.18 -4.24
4pci_ligand -17.81 -8.01 5.57 4.06 -19.43 -3.77 -4.24
4pci_ligand_inverted -14.01 -0.91 2.94 0.43 -16.46 2.87 -3.78
4pci_ligand_inverted -13.95 -0.86 2.77 0.41 -16.27 2.93 -3.78
4pci_ligand_inverted -12.92 -0.78 2.68 0.41 -15.24 3.00 -3.78
4pci_ligand_inverted -12.52 0.70 2.60 0.58 -16.39 4.49 -3.78
4pci_ligand_inverted -13.05 0.31 5.62 0.95 -19.93 4.09 -3.78
The table shown is an excerpt of SEED output table. The total energy term Tot is the sum of the electrostatics and van der Waals energy terms:
$$Tot = ElinW + rec\_des + frg\_des + vdW$$. See Output Files for details about each term in the table.

 [Zhao2014] Zhao H, et al. Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking, Bioorg Med Chem Lett. 24 (2014).