Conformational search Systematic

ERED Systematic search, conformational ligand ensembles [89]... 

In a systematic search there is a defined endpoint to the procedure, which is reached whe all possible combinations of bond rotations have been considered. In a random search, ther is no natural endpoint one can never be absolutely sure that all of the minimum energ conformations have been found. The usual strategy is to generate conformations until n new structures can be obtained. This usually requires each structure to be generate many times and so the random methods inevitably explore each region of the conformc tional space a large number of times. 

Goodman J M and W C Still 1991. An Unbounded Systematic Search of Conformational Space. Journaloj Computational Chemistry 12 1110-1117. 

Finding the minimum of the hybrid energy function is very complex. Similar to the protein folding problem, the number of degrees of freedom is far too large to allow a complete systematic search in all variables. Systematic search methods need to reduce the problem to a few degrees of freedom (see, e.g.. Ref. 30). Conformations of the molecule that satisfy the experimental bounds are therefore usually calculated with metric matrix distance geometry methods followed by optimization or by optimization methods alone. 

J Moult, MNG James. An algorithm for determining the conformation of polypeptide segments m proteins by systematic search. Proteins 1 146-163, 1986. 

Systematic searches exhaustively sample conformational space by sequentially incrementing the torsional angles of aU of the rotatable bonds in a given molecule. This conceptually simple approach is straightforward to implement, but scales exponentially with respect to the number of rotatable bonds. To control the exponential increase in the number of potential conformers obtained, systematic searches are usually combined with tree-based search techniques taken from computer science. Even the best implementations of systematic searches become impractical beyond several rotatable bonds (typically greater than 10). Stochastic searches are based on probabiHstic theories and are better suited to calculations... 

There are also hybrid methods which combine features from two or all three of the above. Opinions will freely be offered about which technique is best , but the reality is that different techniques will perform differently depending on the problem at hand. Except for very simple systems with only one or a few degrees of conformational freedom, systematic methods are not practical, and sampling techniques, which do not guarantee location of the lowest-energy structure (because they do not look everywhere), are the only viable alternative. By default, Spartan uses systematic searching for systems with only a few degrees of conformational freedom and Monte-Carlo methods for more complicated systems. 

Sphere-matching algorithm. Systematic search for conformational, preferences... 

In the MOE environment, molecules are stored in a database with their associated set of conformations. Several methods can be applied to expand the conformational space of organic molecules ranging from molecular dynamics to stochastic methods and systematic search. A fragment-based high-throughput... 

Two classical methods are available in THINK to perform the conformational expansion of molecules systematic search and random search. When the systematic search option is used, the use of contacts check avoids high-energy conformations and reduces the overall processing time. The random method uses a random number generator to select the conformations from within the estimated total number of conformations. The implementation of the program does not prohibit identical conformations to be output resulting from symmetry. These conformations are used in the pharmacophore generation and site search modules. 

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. 

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