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Ramachandran Plot (ramachandran + plot)

Distribution by Scientific Domains

Chemistry	80%

Selected Abstracts

Exploring the binding site of the human muscarinic M3 receptor: Homology modeling and docking study

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 8 2007
Liliana Ostopovici
Abstract The human muscarinic M3 receptor (hM3) and its interactions with selective agonists and antagonists were investigated by means of combined homology and docking approach. Also, two pharmacophoric models for the hM3 agonist and antagonist binding sites were proposed. The three-dimensional (3D) structure of hM3 receptor was modeled based on the high-resolution X-ray structure of bovine rhodopsin from the Protein Data Bank (PDB). To validate the reliability of the model obtained, the main chain torsion angles phi (,) and psi (,) were examined in a Ramachandran plot, and all omega angles were measured for peptidic bond planarity. The characteristics of the active site, the position, and the orientation of ligands in situ, as well as the binding modes of the representative agonists and antagonists, were analyzed by applying a molecular docking technique using the AutoDock 3.0.5 program. Specific interactions responsible for recognition of the hM3 receptor, like ionic bond formed between protonated amine of the ligands and the Asp3.6 side chain were identified. Structure,reactivity relationships have been explained by analyzing the 3D structure of the hM3 model and the ligand conformations resulted from molecular docking simulation. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source]

Revisiting the Ramachandran plot: Hard-sphere repulsion, electrostatics, and H-bonding in the ,-helix

PROTEIN SCIENCE, Issue 11 2003
Bosco K. Ho
Abstract What determines the shape of the allowed regions in the Ramachandran plot? Although Ramachandran explained these regions in terms of 1,4 hard-sphere repulsions, there are discrepancies with the data where, in particular, the ,R, ,L, and ,-strand regions are diagonal. The ,R -region also varies along the ,-helix where it is constrained at the center and the amino terminus but diffuse at the carboxyl terminus. By analyzing a high-resolution database of protein structures, we find that certain 1,4 hard-sphere repulsions in the standard steric map of Ramachandran do not affect the statistical distributions. By ignoring these steric clashes (N···Hi+1 and Oi,1···C), we identify a revised set of steric clashes (C,···O, Oi,1···Ni+1, C,···Ni+1, Oi,1···C,, and Oi,1···O) that produce a better match with the data. We also find that the strictly forbidden region in the Ramachandran plot is excluded by multiple steric clashes, whereas the outlier region is excluded by only one significant steric clash. However, steric clashes alone do not account for the diagonal regions. Using electrostatics to analyze the conformational dependence of specific interatomic interactions, we find that the diagonal shape of the ,R and ,L -regions also depends on the optimization of the N···Hi+1 and Oi,1···C interactions, and the diagonal ,-strand region is due to the alignment of the CO and NH dipoles. Finally, we reproduce the variation of the Ramachandran plot along the ,-helix in a simple model that uses only H-bonding constraints. This allows us to rationalize the difference between the amino terminus and the carboxyl terminus of the ,-helix in terms of backbone entropy. [source]

Ramachandran-type plots for glycosidic linkages: Examples from molecular dynamic simulations using the Glycam06 force field

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2009
Amanda M. Salisburg
Abstract The goals of this article are to (1) provide further validation of the Glycam06 force field, specifically for its use in implicit solvent molecular dynamic (MD) simulations, and (2) to present the extension of G.N. Ramachandran's idea of plotting amino acid phi and psi angles to the glycosidic phi, psi, and omega angles formed between carbohydrates. As in traditional Ramachandran plots, these carbohydrate Ramachandran-type (carb-Rama) plots reveal the coupling between the glycosidic angles by displaying the allowed and disallowed conformational space. Considering two-bond glycosidic linkages, there are 18 possible conformational regions that can be defined by (,, ,, ,) and (,, ,, ,), whereas for three-bond linkages, there are 54 possible regions that can be defined by (,, ,, ,, ,) and (,, ,, ,, ,). Illustrating these ideas are molecular dynamic simulations on an implicitly hydrated oligosaccharide (700 ns) and its eight constituent disaccharides (50 ns/disaccharide). For each linkage, we compare and contrast the oligosaccharide and respective disaccharide carb-Rama plots, validate the simulations and the Glycam06 force field through comparison to experimental data, and discuss the general trends observed in the plots. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source]

Conformational analysis of endomorphin-1 by molecular dynamics methods

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2003
B. Leitgeb
Abstract: Endomorphin-1 (EM1, H-Tyr-Pro-Trp-Phe-NH2) is a highly potent and selective agonist for the ,-opioid receptor. A conformational analysis of this tetrapeptide was carried out by simulated annealing and molecular dynamics methods. EM1 was modeled in the neutral (NH2 -) and cationic (NH -) forms of the N-terminal amino group. The results of NMR measurements were utilized to perform simulations with restrained cis and trans Tyr1 -Pro2 peptide bonds. Preferred conformational regions in the ,2,,2, ,3,,3 and ,4,,4 Ramachandran plots were identified. The g(+), g(,) and trans rotamer populations of the side-chains of the Tyr1, Trp3 and Phe4 residues were determined in ,1 space. The distances between the N-terminal N atom and the other backbone N and O atoms, and the distances between the centers of the aromatic side-chain rings and the Pro2 ring were measured. The preferred secondary structures were determined as different types of , -turns and , -turns. In the conformers of trans -EM1, an inverse , -turn can be formed in the N-terminal region, but in the conformers of cis -EM1 the N-terminal inverse , -turn is absent. Regular and inverse , -turns were observed in the C-terminal region in both isomers. These , - and , -turns were stabilized by intramolecular H-bonds and bifurcated H-bonds. [source]