Conformation flexible

In all of the 3D search methods the conformational flexibility creates considerable difficulties. Large databases of multiple conformations for each structure have been developed which make the solution of this problem possible. 

Hopfinger et al. [53, 54] have constructed 3D-QSAR models with the 4D-QSAR analysis formahsm. This formalism allows both conformational flexibility and freedom of alignment by ensemble averaging, i.e., the fourth dimension is the dimension of ensemble sampling. The 4D-QSAR analysis can be seen as the evolution of Molecular Shape Analysis [55, 56]. 

Further prerequisites depend on the chemical problem to be solved. Some chemical effects have an undesired influence on the structure descriptor if the experimental data to be processed do not account for them. A typical example is the conformational flexibility of a molecule, which has a profound influence on a 3D descriptor based on Cartesian coordinates. In particular, for the application of structure descriptors with structure-spectrum correlation problems in... 

An overview of docking programs is given in Tabic 10.4-3. Depending on the way the conformational flexibility of the ligand is treated, docking can be either rigid or flexible. 

Finally, 3D pharmacophores can be used to provide a naturally partitioned space. By com bining the pharmacophore keys of a set of molecules one can determine how many of th potential 3- or 4- point pharmacophores are accessible to the set and easily identify thos which are not represented. This use of pharmacophores is the basis of a method namei Pharmacophore-Derived Queries (PDQ) [Pickett et al. 1996]. One feature of this particula method is that most molecules will occupy more than one cell (as nearly all molecules wil contain more than one 3-point pharmacophore due to the functionality present an( conformational flexibility). This contrasts with the usual situation, wherein each molecul occupies just one cell. 

GeUiaar D K, G M Verkhivker, P A Rejto, C J Sherman, D B Fogel, L J Fogel and S T Freer 1995 Molecular Recognition of the Inhibitor AG-1343 by HFV-l Protease Conformationally FlexibL Docking by Evolutionary Programming. Chemistry and Biology 2 317-324. 

It is generally recognized that the flexibility of a bulk polymer is related to the flexibility of the chains. Chain flexibility is primarily due to torsional motion (changing conformers). Two aspects of chain flexibility are typically examined. One is the barrier involved in determining the lowest-energy conformer from other conformers. The second is the range of conformational motion around the lowest-energy conformation that can be accessed with little or no barrier. There is not yet a clear consensus as to which of these aspects of conformational flexibility is most closely related to bulk flexibility. Researchers are advised to first examine some representative compounds for which the bulk flexibility is known. 

Proline is relatively compact because of the cyclic nature of its side chain It has less conformational flexibility than the other ammo acids and the presence of proline affects the shape of a peptide more than other ammo acids... 

Conformationally flexible superimposition of these compounds was done to determine their common (phannacophoric) conformation. 

It is obvious, fipom some of the series of substituents in Table 7-11, that the steric constant reflects intuitive notions of group size, and Taft " pointed out close parallels with van der Waals radii. For asymmetrical groups a single van der Waals radius cannot be defined, and the situation is complicated by conformational flexibility. Nevertheless, empirical relationships can be established, and Kutter and Hansch gave Eq. (7-55),... 

Make a sketch of each decalin isomer, and label the orientation of the bridgehead hydrogens with respect to each ring (equatorial or axial). Build a plastic model of each isomer and determine its conformational flexibility (a flexible molecule can undergo a ring flip, but a locked molecule cannot). Is flexibility responsible for stabihty ... 

Conformational flexibility of six-member dihydro N-, O- and S-heterocycles 97IZV2095. 

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