Determination of ligand-binding sites on proteins using long-range hydrophobic potential.
Here we developed a new program, HydrophoBicity On a Protein (HBOP), to find the ligand-binding site of a protein using the long-range hydrophobic-potential function estimated from the experimental data of Israelachvili and Pashley. We calculated the hydrophobic-potential energies at each grid point of a lattice around a protein using the potential function. The hydrophobic potential was evaluated using the carbon atoms of the hydrophobic residues, with the exception of those of the amide groups. We tested HBOP on 26 types of protein (72 protein-ligand complexes), the three-dimensional structures of which were determined experimentally. Although only one hydrophobic function was used, HBOP could successfully identify the binding sites in all of the proteins tested. Moreover, in 24 of the proteins, the binding sites were located in the most hydrophobic region. Surprisingly, the binding sites on sugar binding proteins were the most hydrophobic sites. It implies that the hydrophobic interaction plays an important role in the formation of protein-ligand complexes.
Yamaotsu
Noriyuki
N
Laboratory of Physical Chemistry for Drug Design, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. yamaotsun@pharm.kitasato-u.ac.jp
Oda
Akifumi
A
Hirono
Shuichi
S
D001665:Binding Sites / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D008024:Ligands; D008968:Molecular Conformation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
D008024:Ligands; D011506:Proteins