- Conformation Database
- Database Structure
- Peptide name list: So far 18 biologically active peptides are listed.
- Peptide conformations are categorized into three files:
- Bound, receptor bound conformations for peptides derived from the receptor-ligand complex models. The construction of the complex models are described in method section.
- Dynamics_b, a collection of conformations of peptides obtained by molecular dynamics calculations without using explicit water molecules as solvent. The molecular dynamics calculations were performed on initial peptide structures having a beta-turn conformation at each peptide bond.
- Dynamics_w, a collection of conformations of peptides obtained by molecular dynamics calculations in water bath (not available now).
- Methods
- Receptor-bound structures.
Biologically active endogenous peptides bind active forms of receptors.
The structural models of active form of G protein-coupled receptors can
be constructed from the photochemically activated form of rhodopsin, metarhodopsin
II. The structural model of metarhodopsin II has been constructed from
the crystal structure of rhodopsin together with the other photointermediates
in the rhodopsin photocascade[1]. The structural model of metarhodopsin
II was used as a template for the modeling of the peptide-bound form of
receptors. A method of the model-building of the ligand-receptor complex
has been described from our laboratory[2].
The peptide ligands were manually docked into the ligand-binding cleft of the corresponding receptors. The initial complex model was minimized and then optimized using the molecular dynamics/minimization procedure without constraints between the ligands and the receptors. The molecular dynamics calculations for the backbone amides and side-chains of receptors and the whole structure of the peptides were performed without any constraints between ligands and receptors at 300 K using the cell multipole method, a distance-dependent dielectric constant, and a time step of 1 fsec for 100 psec, sampling at 1 psec intervals using Discover 3 (2000 version, Molecular Simulations Inc.). The hundred conformations were minimized until the final root-mean square deviation (rmsd) was less than 0.1 kcal/mol/angstrom. The lowest energy conformation was selected for the ligand-docking study. The lowest-energy structure was selected as an energy-refined complex model.
- Molecular dynamics calculations.
The molecular dynamics calculations for the peptides were performed at 300 K for 10 nsec after equilibration for 100 psec at 0 through 300 K using the GB/SA conditions in AMBER. The 2000 conformations were sampled at every 5 psec intervals at 300 K.
- References
- M. Ishiguro, Y. Oyama, T. Hirano, Structural Models of the Photointermediates
in the Rhodopsin Photocascade, Lumirhodopsin, Metarhodopsin I, and Metarhodopsin
II. ChemBioChem. 5, 298-310, (2004).(PubMed
14997522)
- M. Ishiguro, Ligand-binding Modes in cationic Biogenic Amine receptors. ChemBioChem. 5, 1210-1219, (2004).(PubMed 15368572)
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