Ligand-flexibility

The grafting of aromatic groups onto the skeletons of aliphatic ligands such as cyclam and/or the addition of other substituents to the ring is generally reflected by loss of ligand flexibility. For example, the restricted... 

Chakrabarti S, Bhattacharyya D, Dasgupta D (2000-2001) Structural basis of DNA recognition by anticancer antibiotics, chromomycin A3 and mithramycin roles of minor groove width and ligand flexibility. Biopolymers 56(2) 85-95... 

In addition, to facihtate the adaptation of the hgand to the RNA binding site, the ligand flexibility might have an additional effect on the recognition... 

Joseph-mccarthy, D., Thomas iv, B.E., Belmarsh, M., Moustakas, D., and Alvarez, J.C. Pharmacophore-based molecular docking to account for ligand flexibility. Proteins Struc., Func. Genet. 

By use of appropriate sterically demanding carboxylates it is possible to generate four-, five-, and six-coordinated mononuclear iron(III) complexes. Ligand flexibility and electronic properties provide fine-tuning. These complexes are subunits of the models for di-iron(II) sites in metallo-proteins mentioned in the following section. 

More recent studies show some variations to the above generalities. 13C and 23Na NMR studies indicate that for Na+ the complexation sequence is 18-crown-6 > 15-crown-5 > benzo-lS-crown-5,482 hinting at the need for ligand flexibility conduction data reveal that for 18-crown-6 the stability sequence is K+>Rb+>Cs+>Na+ 483 extraction studies using metal picrates show that for benzo-15-crown-5, Na+ > K+ > Rb+ > Li+ > Cs+ for 1 1 complexes and that for the corresponding 1 2 complexes K+ > Rb+ > Cs+ 484 further extraction work indicated... 

Coordination of a ligand to a metal reduces the ligand flexibility and therefore the number of conformations available to the metal-ligand system is reduced. 

Another optimization method, related to the least-squares fitting used in point-based algorithms, is the directed tweak method [31]. This is a torsional space optimizer, in which the rotatable bonds of the ligands are adjusted at search time to produce a conformation which matches the 3D query as closely as possible. As directed tweak involves the use of analytical derivatives, it is very fast and allows for an RMS fit to consider ligand flexibility. 

Mekenyan, O., Ivanov, J., Karabunarliev, S., Bradbury, S.P., Ankley, G.T., and Karcher, W., A computationally-based hazard identification algorithm that incorporates ligand flexibility. 1. Identification of potential androgen receptor ligands, Environ. Sci. Tech., 31, 3702-3711, 1997. 

Key words receptor binding site, molecular diversity, ligand flexibility, design strategies... 

The GRIND were designed to be invariant to the position of the ligand in space but not to conformational changes in the ligands. The problem of the ligand flexibility and how to choose the appropriate ligand conformation is extremely difficult. Most 3D QSAR methods published so far are sensitive to the conformation... 

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