Entropy conformational, rule

Side chain generation is often a source of error. It will be most reliable if certain rules of thumb are obeyed. Start with structurally conserved side chains and hold them fixed. Then look at the energy and entropy of rotamers for the remaining side chains. Conventional conformation search techniques are often used to place each side chain. 

Thus Karabatsos concluded that the rationale for Cram s rule was incorrect [10]. In 1967, he published a new model, which took into account the approach of the nucleophile from either side of all three eclipsed conformers [10]. He noted that the enthalpy and entropy of activation for Grignard or hydride additions to carbonyls are 8 to 15 kcal/mole and -20 to -40 eu, respectively. Since the barrier to rotation around the sp -sp carbon-carbon bond is much lower [12], the selectivity must arise from Curtin-Hammett kinetics [13,14]. Of the six possible conformers (Figure... 

A detailed study of crystals of macromolecules 20,21) and their melting under equilibrium conditions revealed that the entropy of fusion, ASf, is often about 7-12 J/(K mol) per mobile unit or "bead" (22). This entropy is linked mainly to the conformational disorder (A and mobility that is introduced on fusion. Sufficiently below the melting temperature, disorder and thermal motion in crystals is exclusively vibrational. While vibrations are small-amplitude motions that occur about equilibrium positions, conformational, orientational, and translational motions are of large amplittide. These types of large-amplitude motion can be assessed by their contributions to heat capacity (23), entropy (22), and identified by relaxation times of the nuclear magnetization 24), Orientational and positional entropies of fusion ASQ ent trans importance to describe the fusion of small molecules. They can be deriv from the many data on fusion of the appropriate rigid, small molecules of nonspheiical and spherical shapes [nonspheiical molecules Walden s rule (1908), ASf = AS j ent AStrans 20-60 J/(K mol) and spherical molecules Richards rule 0 97), ASf = trans = 2-14 J/(K mol)].. The contributions of ASQ ent melting of... 

A detailed analysis of the entropy data on extensive examples using the empirical fusion rules was given by Xenopoluos et al. [34], The three types of disordering that have been studied by these rules are positional [35], orientational [36], and conformational [37-39], which have typical entropy changes of 7-14, 20-50, and 7-12 J/(mol K), respectively [34], Positional and orientational motions are independent of molecular size, whereas conformational motion is proportional to the number of flexible bonds in the molecule. 

A more detailed empirical rule for the entropy of melting is listed at the bottom of Fig. 3.7. Three types of disorder make up the change on fusion positional (pos), orientational (or), and conformational (conf). The approximate contributions to AS are listed in brackets. The first term represents Richards s rule. It is the only contribution for spherical motifs. Irregular motifs can, in addition, show orientational disorder, and thus gain an extra 20-50 J/(K mol) on fusion. Flexible molecules, finally, have a third contribution to the entropy of fusion of 7 -12 J/(K mol) for each flexible bead within the molecule. 

The broad ranges of the values for these contributions indicate that the rules are only approximate. For a complete analysis, other contributions to the entropy of transition must be differentiated, such as changes in volume, electronic states, vibrational states, and structural defects. All these are only partially accounted for in the simple discussion given. Calculating, for example, the conformational part of the entropy in parafGns, one finds that it corresponds to only about 75% of the total entropy of fusion. 

The properties of the latter differ from the properties in bulk, due to the difference in the energetic state of macromolecules in the bulk and at the interface, and due to conformational restrictions imposed on macromolecules by the polymer-air interface which acts as a limiting or reflecting barrier. In the surface layer, the polymer molecules cannot take the same number of conformations as in the bulk. Therefore, an equilibrium state will be attained, either due to the interaction with adjacent chains or as a result of the redistribution in the surface layer of different conformers and their transformation into a more stable state. In the latter case, conformational stabilization is achieved as a result of an energy gain. As a rule, the state of a chain in the surface layer is less statistically probable, and the entropy of the chains is lower. Some properties of the surface layers of polymers at the polymer-air interface are described elsewhere. ... 

Entropy. Molecules with many rotatable bonds pay a large entropic penalty upon binding. In B6hm s scoring function he approximates this by simply multiplying the number of rotatable bonds by a constant. This is a very fast, approximate way to treat this problem. Generating a complete set of conformations for each molecule of interest may not be tractable, and it is not clear whether generating a representative subset of conformations will suffice. It also may be possible to establish a somewhat more precise set of rules based on the principles of conformational analysis. 

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