Cluster hydration model for binding energy calculations of protein-ligand complexes.
We present a new model for predicting the binding affinity in protein-ligand complexes based on an explicit solvent treatment. The model is referred to as the cluster hydration model. Test calculations were performed on complexes of FK506-binding protein (FKBP) and its six ligands. The calculated binding energies had a good correlation with experimental binding affinities; the correlation coefficient r(2) was 0.93. Moreover, we examined the competition between the residue-ligand interactions and the desolvation energies of residues. The results suggested that, for the stabilization of the complexes in solution, the contributions of nonpolar residues at the binding site are larger than those of charged and polar ones because the electrostatic interaction energies between the residues and the ligand were mostly canceled by the desolvation penalties.
Murata
Katsumi
K
Department of Theoretical Drug Design, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501 Japan. murata@pharm.kyoto-u.ac.jp
Fedorov
Dmitri G
DG
Nakanishi
Isao
I
Kitaura
Kazuo
K
D016000:Cluster Analysis; D004735:Energy Transfer; D006860:Hydrogen Bonding; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*
D008024:Ligands; D011506:Proteins