Rigid-searching systems

The AI technique introduced by Tietz and Chu was developed further by Chang and Wyatt (14,15) in their studies of the multiphoton excitation of degenerate anharmonic oscillator-rigid rotor systems (such as tetrahedral and octahedral molecules). Two search strategies were used in these studies. In the first, the best-first strategy, only the most important nodes in each tier are expanded. For example, nodes 1 and 2 in tier 1 of Figure 3 are expanded, yielding nodes 5, 6, and 7 from node 1 and nodes 6 (a repeat) and 8... 

For some purposes, it may be desirable to allow rotation about sp -sp centers (as in biphenyl, for example). These bonds are not generally rotatable, however, so search systems which allow such rotations make it an option. Amide bonds and aromatic bonds are almost always held rigid during CFS searches. 

Because rigid pharmacophoric searching is based on the positions of explicit atoms or points, it is often difficult to pose queries based on directed vectors in space. A specialized search system, CAVEAT, has been developed that permits the specification of queries based on the relative orientation and position of bond vectors in space. If the query bond vectors have been derived from a docked flexible ligand, then when a database of rigid ring-systems (CAST-3D or CSD) is searched, CAVEAT will identify potential substructural skeletons which could act as a rigid mimic of the core substructure of the ligand. 

The computational study of the osmium dihydroxylation of aliphatic al-kenes is much more complicated than the case of aromatic alkenes due to the large number of conformations that the former could adopt. To overcome this issue, we considered the system to be composed of two different parts the catalyst and the olefin. For the catalyst, the conformation considered is that from the X-ray structure. As already shown in the study of styrene [95], and in some experimental works [98], the catalyst is a fairly rigid molecule. For the aliphatic alkenes under study, there is a large number of possible conformations in addition, the stability of an olefin conformation is also affected by the interactions between the olefin substituent and the catalyst. Therefore, the catalyst must be included in the conformational search. The conformational analysis was done using a scheme based on the systematic search approach [99]. The strategy consisted of two parts first we developed a method to identify all of the possible conformations afterwards, we screened all of the possible conformations at MM level to select the most stable. Finally, we only carried out the relatively expensive QM/MM calculations on these selected conformations. 

One concludes from this analysis that the rigid IDM provide an adequate reference frame for describing both external and internal CT processes in a reasonably compact form. However, carrying no information whatever about the reactant interaction, they are - by definition - one-reactant concepts, and therefore may not constitute the optimum collective charge displacement coordinates for reactive systems. In Sections 5.2 and 5.3 we extend this search into... 

Lenhof [47] has developed an approach for docking based on the identification of points on the surface of each molecule that could be equivalenced in a close-packed association. The search for possible rigid-body associations is then speeded up by considering which sets of three points on one molecule could be equivalenced to three points on the other molecule. Suitable docked complexes are then scored in terms of the geometric match between atoms followed by consideration of the chemical complementarity of the match. Trials with docking starting from unbound components showed that for several, but not all, systems the method yielded lists of a few complexes (<10) one of which was dose (<4A rmsd) to the native. This method has been extended to include a treatment of side-chain flexibility in a subsequent screening that is described in 6.6 below [48]. 

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