Flexibility of ligands

The rotational flexibility of ligand subunits such as aryl groups can be suppressed by additional bonds, for example by replacement of a diphenylphosphane unit by a phosphole unit. 

Flexible 3D alignment of a set of ligands binding to the same target and/or CoMFA analysis allowing the perception of a pharmacophore for this target. 

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. 

Proteins, 109,110, 116.Seealso Enzymes Macromolecules average thermal amplitudes, MD simulations, 119 binding of ligands to, 120 dielectric relaxation time of, 122 electrostatic energies in, 122, 123-125 flexibility of, 209,221,226-227, 227 folding, 109,227... 

Glos and Reiser [23] introduced aza-bis(oxazolines) as new chiral ligands for copper and palladium catalysts. Because of the structural flexibility of these compounds they also prepared an immobilized ligand by covalent grafting to methoxypoly(ethyleneglycol) (structures 14 and 15 in Scheme 9). 

Chiral MOFs have to cope with two kinds of challenges when they are used as catalysts. First, in those cases where chirality is induced via sp carbon centers, the incorporation of such centers may confer a degree of flexibility to the framework that eventually impairs the stability after desolvation. Such problems can be circumvented, for instance, using mixed ligand systems where a rigid nonchiral backbone ensures the stability of the structure [82], MOFs with large and flexible chiral ligands... 

Bcl-2 is one of the many factors that control apoptosis, and overexpression of Bcl-2 has been observed in many different cancers. A homology model of Bcl-2 was derived from the NMR 3D structure of the Bcl-XL complex with a Bak BH3 peptide. This model served to search the NCI 3D database of 206,876 organic compounds for potential Bcl-2 inhibitors, which bind to the Bak BH3 binding site of Bcl-2. Full conformational flexibility of the ligands was taken into account in the program DOCK. Thirty-five potential inhibitors were tested, and seven of them had IC50 values from 1.6 to W.OpM. One of... 

Erickson JA, Jalaie M, Robertson DH, Lewis RA, Vieth M. Lessons in molecn-lar recognition the effects of ligand and protein flexibility on molecular docking accuracy. J Med Chem 2004 47 45-55. 

The measurement of these angles for a series of [PdClj(NHC) P(OR)3 ] complexes permitted to evidence the remarkable flexibility of NHCs due to rotations aronnd the iV-substituent bonds [82]. This flexibility, captured by the allows NHCs to respond actively to the steric requirements of co-ligands. This is further confirmed by ab initio molecular dynamics simulations aimed at understanding the variability of ( )j and in a series of NHCs containing Ru-complexes relevant to olefin metathesis [83]. 

---