Conformational transition, barriers

Ab initio methods also appear to be useful for predicting the M- to P-conformational transition barrier for reactive species, such as enolate 8. It is known that the presence of an (iS7-C3-substituent will favor the /17-con former in which the C-3 substituent adopts a pseudoequatorial arrangement. Consequently, deprotonation of C-3 at low temperature of certain benzodiazepines can result in single, conformationally chiral, nonracemic enolates locked in the /(/-configuration. The inversion barrier for enolate 8 at 195 K is calculated by DFT methods to be 17.5 kcal mol-1, which compares with 12.4 kcal mol-1 for the derivative where the N-l group is methyl instead of isopropyl <2003JA11482>. These results were used to explain the enantioselective C-3-alkylation method discussed in... 

Figure 8 shows a one-dimensional sketch of a small fraction of that energy landscape (bold line) including one conformational substate (minimum) as well as, to the right, one out of the typically huge number of barriers separating this local minimum from other ones. Keeping this picture in mind the conformational dynamics of a protein can be characterized as jumps between these local minima. At the MD time scale below nanoseconds only very low barriers can be overcome, so that the studied protein remains in or close to its initial conformational substate and no predictions of slower conformational transitions can be made. 

Fig. 10. Conformational flooding accelerates conformational transitions and makes them accessible for MD simulations. Top left snapshots of the protein backbone of BPTI during a 500 ps-MD simulation. Bottom left a projection of the conformational coordinates contributing most to the atomic motions shows that, on that MD time scale, the system remains in its initial configuration (CS 1). Top right Conformational flooding forces the system into new conformations after crossing high energy barriers (CS 2, CS 3,. . . ). Bottom right The projection visualizes the new conformations they remain stable, even when the applied flooding potentials (dashed contour lines) is switched off.

The barrier for conversion of the skew conformation to the s-trans conformation is 3.9kcal/mol. This energy maximum presiunably refers to the conformation (transition state) in which the two n bonds are mutually perpendicular. Various MO calculations find the s-trans conformation to be 2-5 kcal/mol lower in energy than either the planar or skew cisoid conformations. Most high-level calculations favor the skew conformation over the planar s-cis, but the energy differences found are quite small. ... 

The three-dimensional structures, or part of it, are also known for Desulfovibrio vulgaris and Anacystis nidulans flavodoxins. These results, including those obtained on C.MP., were recently summarized by Adman . Hence, these results will be discussed only briefly. The x-ray structures show that the isoalloxazine ring is embedded in a hydrophobic pocket of the apoprotein, i.e. flanked by at least one aromatic amino acid residue. During the redox transitions, especially from the oxidized to the semiquinone state, small conformational changes occur and contacts with the isoalloxazine ring are formed or broken. These conformational transitions form probably a kinetic barrier so that the semiquinone state is trapped by the apoprotein and, therefore, rather stable towards oxidation by molecular oxygen. 

The value of q3 = (6) V2R (R is the CC bond length) is 0.63 A. Under pseudorotation the equatorial boat-shaped structures B (0 = 90°, = 0, 60°, 120°,.. . ) turn into a twist-boat structure TB (0 = 90°, = 30°, 90°,.. . ). The transitions between the chair and twist boat structures involve the intermediate formation of half boat (HB) and half chair (HC) structures. Quantum chemical calculations carried out by Dixon and Komornicki [1990] show that the axial structure C with symmetry D3d is stable. The energies of structures B and TB are 7.9 and 6.8kcal/mol higher than C. The barrier for transition from C to TB is 12.2-12.4 kcal/ mol. Because of the high barriers for pseudorotation, only thermally activated conformational transitions occur in cyclohexane. 

Heijboer [28] has reported the dynamic mechanical properties of poly(nethacrylate)s with different size of the saturated ring as side chain. The y relaxation in these polymers is attributed to a conformational transition in the saturated ring. In the case of poly(cyclohexyl methacrylate), the transition is between the two chair conformations in the cyclohexyl ring. However, this type of internal motion in hindered by rather high intramolecular barriers, which can reach about 11 kcal mol-1. 

The antiperiplanar, lone-pair hypothesis is based on the presumption that the lifetime of a tetrahedral intermediate in hydrolysis is shorter than the average time of rotation about the C-O bond that is, the barrier of conformational transition exceeds the reaction barrier. However, a simple intermediate (hydrogen orthoester) has been detected, and on this basis, the antiperiplanar, lone-pair theory was questioned.Similarly, studies on the hydrolysis of saccharide derivatives 4os indicated that the departure of... 

The crystal structure of the dark state of asCp has recently been released [58], and as predicted it is in the trans conformation. However the chromophore has only one covalent link to the protein. Fragmentation of the protein has occurred -this has been shown to be an intrinsic step in the maturation of the asCP chromophore. The cleavage of the Cys62-chromophore bond (asCP numbering) may provide the chromophore freedom of movement not observed in GFP and other GFP-like proteins - by lowering the activation barriers for cis/trans conformational transitions it may be responsible for asCP kindling abilities. 

Different mechanisms for the spontanous generation of prions in familial human TSEs through point mutations in PrP have been postulated (Cohen, 1999). A mechanism that has been discussed for many years proposes tliat the single amino acid replacements within mature PrP either decrease the thermodynamic stability of PrP and thereby facilitate its conversion to PrP = (Cohen et al, 1994 Huang et al, 1995) and/or increase the stability of PrP (Cohen, 1999). A second model suggests that the mutations accelerate the formation PrP <= by decreasing the activation energy barrier for the conformational transition (Cohen,... 

The last line in Table I presents decay parameters for a dimer in which all 10 hydroxyl groups have been acetylated. Acetylation reduces Ti and T2, but there is not much change in and a 2. More importantly, acetylation increases the size of the energy barrier that must be surmounted when the dimer undergoes the conformational transition from one rotational isomer to the other. For this reason, the rate of intramolecular conformational change is much slower in the peracetylated dimer than in the free phenol forms it is slow enough so that 400-MHz proton NMR can resolve distinct signals from the two rotational isomers in dioxane-ds solution 10). The... 

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