Rotatable bonds

A.s mentioned above, most molecules ean adopt more than one conformation, or molecular geometry, simply by rotation around rotatable bonds. Thus, the different conformations of a molecule can be regarded as different spatial arrangements of the atoms, but with an identical constitution and configuration, They are interconvertible and mo.stly they cannot be i.solatcd separately. Figure 2-101 show-s a. super-imposition of a set of conformations of 2R-benzylsuccinatc (cf. Figure 2-89). 

As the number of conformations increases exponentially with the number of rotatable bonds, for most molecules it is not feasible to take all possible conformations into account. However, a balanced sampling of the conformational space should be ensured if only subsets arc being considered. In order to restrict the number of geometries output, while retaining a maximum of conformational diversity, ROTATE offers the possibility of classifying the remaining conformations, i.c., similar conformations can be combined into classes. The classification is based on the RMS deviation between the conformations, either in Cartesian (RMS y 7if [A]) or torsion space in [ ], The RMS threshold, which decides whether two... 

In Eq. (16 i denotes an atom up to lour non-rotatable bonds away from the proton and is the total number of those atoms. A bond is deRned as non-rotatable if it belongs to a ring, to a. T-system, or to an amide functional group q- is the partial atomic charge of the atom i, and is the 3D distance between the proton j and the atom i. Figure 10.2-5 shows an example of a proton RDF descriptor. 

Shielding and unshiclding by. single bonds were encoded using Eq, (IS), where i is a single bond up to the seventh sphere (S,7j) of non-rotatable bonds centered on the proton, and and are distance and angle, respectively (Figure 1().2-6b). 

Prediction of various physicochemical properties such as solubihty, lipophhicity log P, pfQ, number of H-donor and acceptor atoms, number of rotatable bonds, polar surface area), drug-likeness, lead-likeness, and pharmacokinetic properties (ADMET profile). These properties can be applied as a filter in the prescreening step in virtual screening. 

The chromosome in a genetic algorithm codes for the torsion angles of the rotatable bonds. 

As seen in the previous section, if two identical knees of the (L,0)-(L, L ) family are connected together symmetrically with respect to a connecting plane, and if this connecting process is continued while maintaining the knees in a common plane, the structure obtained will close to a torus which will be completed after 10 fractional turns (Figs 7 and 9), However, if a rotational bond shift is introduced... 

Fig. 10. (a) Planar representation of a single rotational bond shift at the (9,0) to (9,0) connection of two (9,0)-(5,5) knees. This leads to a 27r/9 rotation out of the upper knee plane (b) single bond shift at the (5,5) to (5,5) connection of two (9,0)-(5,5) knees. This leads to a InjS rotation, out of the lower knee plane. The arrow indicates the location of the bond shift. 

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