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Conformational Regions (conformational + regions)

Distribution by Scientific Domains

Chemistry	75%

Selected Abstracts

Using the local elevation method to construct optimized umbrella sampling potentials: Calculation of the relative free energies and interconversion barriers of glucopyranose ring conformers in water

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2010
Halvor S. Hansen
Abstract A method is proposed to combine the local elevation (LE) conformational searching and the umbrella sampling (US) conformational sampling approaches into a single local elevation umbrella sampling (LEUS) scheme for (explicit-solvent) molecular dynamics (MD) simulations. In this approach, an initial (relatively short) LE build-up (searching) phase is used to construct an optimized biasing potential within a subspace of conformationally relevant degrees of freedom, that is then used in a (comparatively longer) US sampling phase. This scheme dramatically enhances (in comparison with plain MD) the sampling power of MD simulations, taking advantage of the fact that the preoptimized biasing potential represents a reasonable approximation to the negative of the free energy surface in the considered conformational subspace. The method is applied to the calculation of the relative free energies of ,- D -glucopyranose ring conformers in water (within the GROMOS 45A4 force field). Different schemes to assign sampled conformational regions to distinct states are also compared. This approach, which bears some analogies with adaptive umbrella sampling and metadynamics (but within a very distinct implementation), is shown to be: (i) efficient (nearly all the computational effort is invested in the actual sampling phase rather than in searching and equilibration); (ii) robust (the method is only weakly sensitive to the details of the build-up protocol, even for relatively short build-up times); (iii) versatile (a LEUS biasing potential database could easily be preoptimized for small molecules and assembled on a fragment basis for larger ones). © 2009 Wiley Periodicals, Inc. J Comput Chem 2010 [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]

Site-directed PEGylations of Thymosin , 1 Analogs and Evaluation of Their Immunoactivity

CHINESE JOURNAL OF CHEMISTRY, Issue 4 2009
Jiankun QIE
Abstract PEGylation is an effective way to improve the pharmacokinetic profiles of pharmaceutical proteins or peptides. But the relatively large and long PEG chains would be likely to shelter the active site of a small peptide because of its small size, compared with a protein. Therefore, the positions and numbers of PEGylation are crucial for the bioactivity of a PEGylated peptide. To elucidate the relationship between the PEGylated positions and bioactivity of a peptide drug, site-specific PEGylations were performed on Zadaxin (Thymosin , 1, T,1), which is a pharmaceutical peptide with an , -helix region, a , -turn region, and random coils. Site-specific mono-PEGylations of T,1 in different conformational regions were realized through introducing one cysteine residue into the desired positions of the peptide, followed by a coupling reaction with a thiol-attached maleimide-PEG reagent. Primary data from IFN- , production of splenocytes induced by Con A showed that the influence of PEGylation on Zadaxin was position-dependent, and mostly, positive effects were observed after PEGylation, which indicated that the position of PEGylation is important for maintaining the bioactivity of a peptide. [source]