title: Importance of CH/π hydrogen bonds in recognition of the core motif in proline-recognition domains: an ab initio fragment molecular orbital study.
abstract: We examined CH/π hydrogen bonds in protein/ligand complexes involving at least one proline residue using the ab initio fragment molecular orbital (FMO) method and the program CHPI. FMO calculations were carried out at the Hartree-Fock (HF)/6-31G*, HF/6-31G**, second-order Møller-Plesset perturbation (MP2)/6-31G*, and MP2/6-31G** levels for three Src homology 3 (SH3) domains and five proline-recognition domains (PRDs) complexed with their corresponding ligand peptides. PRDs use a conserved set of aromatic residues to recognize proline-rich sequences of specific ligands. Many CH/π hydrogen bonds were identified in these complexes. CH/π hydrogen bonds occurred, in particular, in the central part of the proline-rich motifs. Our results suggest that CH/π hydrogen bonds are important in the recognition of SH3 and PRDs by their ligand peptides and play a vital role in the signal transduction system. Combined use of the FMO method and CHPI analysis is a valuable tool for the study of protein/protein and protein/ligand interactions and may be useful in rational drug design.
authors.affiliation: Central Research Laboratory, Kissei Pharmaceutical Company Ltd, Azumino-city, Nagano, 399-8304, Japan. tomonaga_ozawa@pharm.kissei.co.jp
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Ozawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okazaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitaura
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D030562:Databases, Protein; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D008024:Ligands; D010455:Peptides; D011506:Proteins; D011392:Proline