Another variant of WaterLOGSY method called LOGSY utilizes the titration slopes as a measure of solvent accessibility. The titration slopes are created by a constant increase of protein concentrations. This method also provides more insight into the process of ligand solvation by checking the influence of protein concentration onto the process. This approach was used on the bromodomain 1 of protein 4 (Brd4-BD1) by mapping epitopes of two ligands interacting with Brd4-BD1 and predicting ligands position. The results showed that the triazolopyridazine moiety of both ligands was implanted into the binding pocket of the Brd4. Additionally, the results from LOGSY titration showed that methyl-group 1 of ligand 1, aromatic proton 8 of ligand 2 and aromatic proton 8 of ligand 1 exhibit strong water NOE. This information enabled researchers to utilize a chemical replacement strategy (substitute bound water molecules by suitable functional groups) for aromatic proton 8 in a series of ligands containing the triazolopyridazine ring. Those protons were replaced with an amino or aminomethyl groups and as a result, the binding affinity of those ligands increased 100-fold. Finally, the results obtained from X-ray crystallography for ligands with such modifications allowed to find the binding mode of the triazolopyridazine ring of ligand 1 (with methyl group pointing internally) and the substituted amino group was found to create hydrogen bond to the side chain of Asn140 of Brd4-BD1 [402].