Steric clashes

In the next step, the suggested models are translated into 3D space by subsequently combining the templates. Again, each model is assessed and ranked according to various structural criteria, such as the geometric fit of the 3D templates and non-bonding interactions (steric clashes). If none of the solu-... 

During this process of designing sequence changes, models were built and assessed to ensure that there were no obvious steric clashes and that the hydrophobic core was well packed. Furthermore, secondary structure prediction was also used to monitor the progress of change and to choose among different possible substitutions. The final sequence (see Table 17.3) contains 28 changes it had 50% identity to B1 and the similarity to Rop had increased from 5.4% identity to 41%. 

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 Liskamp group also examined the ability of peptoid-peptide hybrids to be bound by the MHC Class II receptor, an important component of the human immune system [39]. Two of three peptoid substitutions in the 14-residue peptide caused substantial decreases in binding affinity, despite the fact that these were solvent-exposed residues. These results were attributed to a loss of hydrogen-bond contacts as well as to steric clashes caused by unfavorable positioning of the new side chain groups. 

What is the origin of the energy difference between the polyproline II and /J-strand backbone conformations Brant and Flory (1965b) emphasize the important roles of steric clash, dipole-dipole interactions (see also Avbelj and Moult, 1995), and the torsional potentials governing rotation about the backbone ,t/i angles (see also Flory, 1969). An ab initio quantum mechanics study (Han et al., 1998 see also references therein to earlier work) finds that solvation by water is important. The authors examine the predicted stabilities of eight conformers of... 

Of course, we do not mean to imply any kind of moral imperative here. For example, if you were checking out some dubious looking starting material that supposedly contained a given functionality (e.g., Ar-CH2-Br with no ortho substituent on the aryl ring and no other obvious steric clash between this aryl system and any other), then it would be quite acceptable - and even desirable - to exploit some obvious handle in the form of a cutdown interpretation . In this case for example, if there is no two-proton singlet (or AB system if the molecule is chiral) at around 4.6-4.3 ppm, then you can reasonably conclude that the stuff is not what you wanted. Job done. Move on. 

An important difficulty of this simulation is the fact that, once the two helices are close to each other, it is very difficult to slide one with respect to the other or change their relative orientation because of steric clashes. This means that a simulation where the helix-helix distance is constrained would not be able to sample phase space efficiently but rather would remain near the local energy minimum where it started. In contrast, using ABF, the helices have the opportunity to move closer and farther apart so that their relative position can vary more freely. 

If the a-meso regioselectivity of hydroxylation is not inherent to the heme group, as indicated by the fact that all four isomers are obtained by coupled heme oxidation (40), how is the regiochemistry of heme oxidation influenced by electronic factors One possibility is that the puckering or ruffling of the porphyrin caused by steric clashes between the meso and flanking substituents in the meso-substituted heme probes... 

A hypothetical conformational state defined by a geometrically and electronically strained site within an enzyme thought to facilitate the conversion of an enzyme-substrate complex to the transition state. Vallee and Williams defined the entatic state as an abnormal condition of localized strain transmitted by relief of compression or other steric clashes elsewhere in the enzyme. They suggested that catalytic rate enhancements arise from the heightened reactivity of catalytic group(s) that have experienced unimolecular activation. Williams ... 

The favoured dihedral angles for protein main chains were derived from energy considerations of steric clashes in peptides giving the well known Ramachandran plot (Ramachandran and Sasisekharan, 1968). These phi/psi combinations characterize the elements of secondary structure. Accurate main chain models can be constructed from spare parts, that is short pieces of helices, sheets, turns, and random coils taken from highly refined structures, provided a series of C-alpha positions can be established from the electron density map... 

Recently, a selection of fungal 1,4-p-glucosidases was probed with mono-0-methyl derivatives of 4-nitrophenyl p-D-glucopyranoside, and it was discovered that only mono-O-methylation of 0-6 (28) was tolerated to a varying extent, whereas none of the substrate analogues (9-methylated at a secondary position was a substrate of these enzymes.109 Steric clashes with the active site were invoked to rationalize these findings. 

Observed adducts arise through exo addition of the lactone to the re-re face of the nitrone 141, which avoids an unfavorable C=0/0-ferf-butyl steric clash. 

Langlois and co-workers (179) found the same exo stereochemical preference through double asymmetric induction of a related ene-lactone (1 )-145 with their well-explored and efficient camphor-derived oxazoline nitrone (150-146 (Scheme 1.32). They found the cycloaddition components form a matched pair and allowed kinetic resolution of the racemic lactone in up to 70% enantiomeric excess (ee). They suggest the selectivity for exo adduct 147 arises through destabilization of the endo transition state by a steric clash between dipolarophile ring hydrogens and the bornane moiety. 

Grigg and co-workers (310) recently examined the 1,3-APT reaction of various aldoximes (270) (R or R = H) with divinyl ketone (Scheme 1.56). While ketoximes 270 (R = R) form a mixture of adducts, 271 and 272 via nitrone 273, the aldoximes selectively afford 272 (as a mixture of endo and exo diastereoisomers). Under the thermal reaction conditions, the oxime starting materials can undergo ( /Z) isomerization, while the nitrone intermediate was expected to be unaffected and the isolated cycloadducts showed no interconversion via cycloreversion. Thus, the increasing selectivity for endo-212 [via ( )-273, R = H] over exo-212 [via (Z)-273, R = H] with the increasing size of the aldoxime substituent was attributed primarily to the inhibition of oxime isomerization by steric clash between R or R and the oxime OH. In contrast, Lewis acid catalysis, in particular by hafnium (iv) chloride, of the cycloaddition of various aldoximes with this dipolarophile gave exo-271 exclusively (216). 

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