Conformation computational studies

Helms and McCammon 1997] Helms, V., McCammon, J.A. Kinase Conformations A computational study of the effect of ligand binding. Prot. Sci. 6 (1997) 2336-2343... 

Figure 4.49 reprinted with permission from Pranata J and W L Jorgensen. Computational Studies on FK506 Conformational Search and Molecular Dynamics Simulations in Water. The Journal of the American Chemical Society 113 9483-9493. 1991 American Chemical Society. 

Polymers can be crystalline, but may not be easy to crystallize. Computational studies can be used to predict whether a polymer is likely to crystallize readily. One reason polymers fail to crystallize is that there may be many conformers with similar energies and thus little thermodynamic driving force toward an ordered conformation. Calculations of possible conformations of a short oligomer can be used to determine the difference in energy between the most stable conformer and other low-energy conformers. 

The C2 symmetry of sulfide 13 means that a single diastereomer is formed upon alkylation (Scheme 1.10). Attack from the Si face of the ylide is preferred as the Re face is shielded by the methyl group cis to the benzylidene group (28). Metzner postulates that this methyl group also controls the conformation of the ylide, as a steric clash in 27b renders 27a more favorable [16]. However, computational studies by Goodman revealed that 27a was not particularly favored over 27b, but it was substantially more reactive, thus providing the high enantioselectivity observed... 

The structures and conformational properties of a simple hemicarcerand, created earlier by Cram, see <96JA5590>, as well as the complexation and decomplexation with guest molecules have been computationally studied <96JA8056>. 

In one of the very first realistic computational studies of PECD effects, performed for the amino acid alanine [51], it was noted that different results were obtained at each of three fixed geometries corresponding to low lying conformations identified in previous structure investigations [69-71]. A later combined experimental-theoretical study of PECD in 3-hydroxytetrahydrofuran [61] further looked at the influence of presumed conformation and concluded that while the predicted cross-section, a, and p parameters were mildly affected by conformation, the chiral parameters were much more strongly... 

The reaction shows a dependence on the E- or Z-stereochemistry of the enolate. Z-enolates favor anti adducts and E-enolates favor syn adducts. These tendencies can be understood in terms of an eight-membered chelated TS.299 The enone in this TS is in an s-cis conformation. The stereochemistry is influenced by the s-cis/s-trans equilibria. Bulky R4 groups favor the s-cis con former and enhance the stereoselectivity of the reaction. A computational study on the reaction also suggested an eight-membered TS.300... 

The conformational properties of various 1,1 -diheteroferrocenes (7-10) have been the subject of three computational studies using extended Huckel methods.19,46 471,1 -Diphosphaferrocene has also been studied using the Fenske-Hall approach.48 and an MS Xa method.46 Where they overlap, the four treatments are in reasonable qualitative agreement. 

Many of the conformational properties of peptide systems, including protein conformation, can be approximated in terms of the local interactions encountered in dipeptides, where the two torsional angles 4> (N-C(a)) and < i (C(a)-C ) are the main conformational variables. N-acetyl N -methyl alanine amide, shown in Fig. 7.11, is a model dipeptide that has been the subject of numerous computational studies. 

As is well known, the conformational properties of cyclohexane form one of the classical problems of conformational analysis (104) and have been the subject of numerous earlier computational studies (11, 41, 82,105-107). Cyclohexane shows a variety of very interesting conformational properties which make it an ideal candidate for illustrating key features of conformational calculations. 

As seen above, /3-deprotonation implies a six-center transition state. Recent computational studies show an important variation of the H —C—C—O dihedral angle from reactant to transition state . Thus, the ground state geometry of the oxirane cannot be used to predict its reactivity. However, for structural reasons, some oxiranes cannot adopt a suitable conformation for -deprotonation and furnish exclusively a-deprotonation products. This concept is well illustrated by the norbornene oxide 17, which gives exclusively the transannular 1,3 insertion product 18 in the presence of lithium amide (Scheme 5) . 

The MacMillan laboratory has produced an interesting study on the reductive amination of a broad scope of aromatic and aliphatic methyl ketones catalyzed by ent-lk, utilizing Hantzsch ester as a hydride source (Scheme 5.26) [48]. Apphcation of corresponding ethyl ketones gave very low conversions. Computational studies indicated that while catalyst association with methyl ketones exposes the C=N Si face to hydride addition, substrates with larger alkyl groups are forced to adopt conformations where both enantiofaces of the iminium ir... 

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