Cl-pi interactions in protein-ligand complexes.
During systematic analysis of nonbonded contacts in protein-ligand complexes derived from crystal structures in the Protein Data Bank, Cl-pi interactions have been found, not only in the well-documented serine proteases but also, to a lesser extent, in other proteins. From geometric analysis of such Cl-pi interactions in the crystal structures, two distinct geometries were found: the "edge-on" approach of a Cl atom to a ring atom or C-C bond and the "face-on" approach toward the ring centroid with an average interatomic distance of 3.6 A. High-level ab initio calculations using benzene-chlorohydrocarbon model systems elucidated that the calculated Cl-pi interaction energy is -2.01 kcal/mol, and the dispersion force is the major source of attraction. We also discussed the geometric flexibility in Cl-pi interactions and a relationship between the intensity of the pi density in an aromatic ring and the interaction position of the Cl atom.
Imai
Yumi N
YN
Department of Theoretical Drug Design, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. imai_yumi@takeda.co.jp
Inoue
Yoshihisa
Y
Nakanishi
Isao
I
Kitaura
Kazuo
K
D004583:Electrons; D008024:Ligands; D011506:Proteins / Q000737:chemistry*
D008024:Ligands; D011506:Proteins