Conformational isomerism

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

Simulations of biomolecules: characterization of the early steps in the pH-induced conformational conversion of the hamster, bovine and human forms of the prion protein

Abstract: As computer power increases, so too does the range of interesting biomolecular phenomena and properties that can be simulated. It is now possible to simulate complicated protein conformational changes at ambient or physiological temperatures. In this regard, we are attempting to map the conformational transitions of the normal, cellular prion protein (PrP C ) to its infectious scrapie isoform (PrP Sc ), which causes neurodegenerative diseases in many mammals. These two forms have identical sequences and are conformational isomers, with heightened formation of β–sheet structure in the scrapie form. Conversion can be triggered by lowering the pH, but thus far it has been impossible to characterize the conformational change at high resolution using experimental methods. Therefore, to investigate the effect of acidic pH on PrP conformation, we have performed molecular–dynamics simulations of hamster, human and bovine forms of the prion protein in water at neutral and low pH. In all cases the core of the protein is well maintained at neutral pH. At low pH, however, the protein is more dynamic, and the sheet–like structure increases both by lengthening of the native β–sheet and by addition of a portion of the N–terminus to widen the sheet by another 2–3 strands.

Anomeric and Mesomeric Effects in Methoxycarbonylsulfenyl Chloride, CH3OC(O)SCl: An Experimental and Theoretical Study †

Abstract: The molecular structure and conformational properties of methoxycarbonylsulfenyl chloride, CH 3 OC(O)SCl, were determinated in the gas and solid phases by gas electron diffraction, low-temperature X-ray diffraction, and vibrational spectroscopy. Furthermore, quantum chemical calculations were performed. Experimental and theoretical methods result in structures with a planar C-O-C(O)-S-Cl skeleton. The electron diffraction intensities are reproduced best with a mixture of 72(8)% syn and 28(8)% anti conformers (S-Cl bond synperiplanar/antiperiplanar with respect to C=O bond) and the O-CH 3 bond synperiplanar with respect to the C=O bond. The syn form is the preferred form and becomes the exclusive form in the crystalline solid at low temperature. This experimental result is reproduced very well by Hartree-Fock approximation and by density functional theory at different levels of theory but not by the MP2/6-311G * method, which overestimates the value of ΔG° between the syn and anti conformers. The results are discussed in terms of anomeric effects and a natural bond orbital (NBO) calculation. Photolysis of matrix-isolated CH 3 OC(O)SCl with broad-band UV-visible irradiation produces an interconversion of the conformers, and the concomitant decomposition leads to formation of OCS and CO molecules.

Conformational analysis of L-prolines in water.

Abstract: The results of the ring conformational analysis of l-proline, N-acetyl-l-proline, and trans-4-hydroxy-l-proline by NMR combined with calculations using density functional theory (DFT) and molecular dynamics (MD) are reported. Accurate values of 1H−1H J-couplings in water and other solvents have been determined. Using a two-site equilibrium model, the Cγ-endo conformer of l-proline in water has been identified as intermediate between γTδ [twist(Cγ-endo, Cδ-exo)] and γE [envelope(Cγ-endo)] and the Cγ-exo conformer as βTγ. Both conformers were equally populated at room temperature. The N-acetyl [cis-rotamer γTβ(80%)/γE(20%) and trans-rotamer γTβ(61%)/γE(39%)] and 4-hydroxy (γE) derivatives showed significant changes in both the population and the geometries of the preferred ring conformers. The combination of NMR predicted populations with the DFT B3LYP/6-311+G(2d,p)/IEFPCM calculations proved successful, resulting in fairly accurate predictions of J-couplings. Simulations using MD were mostly in favor of th...

Multiple conformational states of a Pro-Pro peptide. Solid-state and solution conformations of Boc-Aib-Pro-Pro-NHMe

Abstract: The solid-state and solution conformations of the model peptide Boc-Aib-Pro-Pro-NHMe have been studied by X-ray diffraction and NMR. The peptide adopts a poly(pro1ine 11) conformation in the solid state. Two molecules are observed in the asymmetric unit differing in the geometry (cisltrans) of the urethane group. The molecules are held together in the crystal by a complex network of hydrogen bonds involving three molecules of water, which cocrystallize. Dissolution of single crystals at low temperature (\sim 233 K) permits NMR observation of the solid-state conformer. In solution, the peptide undergoes a trans-cis isomerization of the Pro-Pro bond. Low- temperature NMR measurements allow the detection of three conformational states of the Pro-Pro segment. Both cis’ and trans’ rotational isomers about the $C^\alpha -CO$ $(\psi)$ bond of Pro-3 are detectable at low temperatures. Theoretical calculations suggest an appreciable activation barrier to $\psi$ rotation. Temperature and solvent dependence of NH chemical shifts provide evidence for an intramolecular hydrogen bond, involving the NHMe group in the cis Pro-Pro conformer. Energy calculations suggest the possibility of a type VI $\beta$-turn conformation stabilized by a 4 $\rightarrow$ 1 hydrogen bond between the Aib-1 CO and NHMe groups.