Conformational isomerism

About: Conformational isomerism is a research topic. Over the lifetime, 11563 publications have been published within this topic receiving 199312 citations.

Dynamics of the nitroxide side chain in spin-labeled proteins.

Abstract: The dynamics of the tether linking methanethiosulfonate (MTSSL) spin probes to α-helices has been investigated with the purpose of rationalizing its effects on ESR line shapes. Torsional profiles for the chain bonds have been calculated ab initio, and steric interactions with the α-helix and the neighboring residues have been introduced at the excluded-volume level. As a consequence of the restrictions deriving from chain geometry and local constraints, a limited number of allowed conformers has been identified that undergo torsional oscillations and conformational jumps. Torsional fluctuations are described as damped oscillations, while transition rates between conformers are calculated according to the Langer multidimensional extension of the Kramers theory. The time scale and amplitude of the different motions are compared; the major role played by rotations of the outermost bonds of the side chain emerges, along with the effects of substituents in the pyrroline ring on the conformer distribution and d...

Systematic ab initio studies of the conformers and conformational distribution of gas-phase tyrosine.

Abstract: A full structural assignment of the conformers of gaseous tyrosine is presented. A total of 1296 unique trial structures were generated by allowing for all combinations of internal single-bond rotamers and optimized at the B3LYP∕6-311G* level of theory and then subjected to further optimization at the B3LYP∕6-311++G** level. A total of 76 conformers are found and their dipole moments, rotational constants, and harmonic frequencies are determined. Accurate relative energies are given at the MP2∕6-311G(2df,p)∕∕B3LYP∕6-311++G** level of theory. Characteristic H-bonding types are classified and listed for all the conformers. The four most stable conformers display an intramolecular H bond, COOH⋯NH2, and an additional H-bonding interaction between the amino group and π electron of the aromatic ring. The results further confirm that the global minimum conformations of the aromatic amino acids have the same H-bonding type. Combined with statistical mechanics principles, conformational distributions at various te...

Ab Initio Study of Trimethyl Phosphate: Conformational Analysis, Dipole Moments, Vibrational Frequencies, and Barriers for Conformer Interconversion

Abstract: Ab initio molecular orbital calculations on trimethyl phosphate (TMP) were done using 6-31G* and 6-31G** basis sets, both at RHF and MP2 levels of theory. We located three minima corresponding to C3, C1, and Cs symmetries, given in order of increasing energies. At the MP2/6-31G** level, the energy difference between the C3 and C1 conformers was 0.56 kcal/mol, while that between the C3 and Cs was 1.43 kcal/mol. Our observations are at variance with an earlier ab initio calculation, employing smaller basis sets, STO-3G* and 4-31G*, which had reported that the C1 conformer was the lowest in energy. Furthermore, the earlier calculation did not report the occurrence of a minimum corresponding to the Cs symmetry. Vibrational frequency calculations were done at the HF and MP2 levels. The computed frequencies were found to compare well with experimental vapor phase and matrix isolation data reported earlier, leading to a definitive assignment of the infrared features of TMP. The barrier for conformer interconvers...

Two folded conformers of ubiquitin revealed by high-pressure NMR.

Abstract: High-pressure 15N/1H two-dimensional NMR spectroscopy has been utilized to study conformational fluctuation of a 76-residue protein ubiquitin at pH 4.5 at 20 degrees C. The on-line variable pressure cell technique is used in conjunction with a high-field NMR spectrometer operating at 750 MHz for 1H in the pressure range between 30 and 3500 bar. Large, continuous and reversible pressure-induced 1H and 15N chemical shifts were observed for 68 backbone amide groups, including the 7.52 ppm 15N shift of Val70 at 3500 bar, indicating a large-scale conformational change of ubiquitin with pressure. On the basis of the analysis of sigmoid-shaped pressure shifts, we conclude that ubiquitin exists as an equilibrium mixture of two major folded conformers mutually converting at a rate exceeding approximately 10(4) s(-1) at 20 degrees C at 2000 bar. The second conformer exists at a population of approximately 15% (DeltaG(0) = 4.2 kJ/mol) and is characterized with a significantly smaller partial molar volume (DeltaV(0) = -24 mL/mol) than that of the well-known basic native conformer. The analysis of 1H and 15N pressure shifts of individual amide groups indicates that the second conformer has a loosened core structure with weakened hydrogen bonds in the five-stranded beta-sheet. Furthermore, hydrogen bonds of residues 67-72 belonging to beta5 are substantially weakened or partially broken, giving increased freedom of motion for the C-terminal segment. The latter is confirmed by the significant decrease in 15N[1H] nuclear Overhauser effect for residues beyond 70 at high pressure. Since the C-terminal carboxyl group constitutes the reactive site for producing a multi-ubiquitin structure, the finding of the second folded conformer with a substantially altered conformation and mobility in the C-terminal region will shed new light on the reaction mechanism of ubiquitin.