Molecular dynamics simulation of CREBBP bromodomain in complex with ligand US13A

This 0.4-microsecond run of the complex of the CREBBP bromodomain with US13A, a nanomolar ligand identified with AutoCouple (compound 16 in the AutoCouple paper), shows a transient rotation of the tail-group. In contrast, the head group, i.e., the acetophenone moiety which mimics the natural ligand, shows stable interactions with the side chain of the conserved asparagine and tyrosine. Other residues highlighted are involved in hydrophobic interactions that stabilize the compound in the pocket. The furan moiety of the tail group and the arginine interact through π stacking. CREBBP residues Asn1168, Tyr1125, Leu1120, Ile1122, Val1174 and Arg1173 are represented as sticks with cyan carbon atoms.