Flexibility, ligand, increased

In principle, every conformer of a set of flexible ligands could be stored in a database, and then each conformation could be evaluated with rigid-body docking algorithms. The size of the ensemble is critical since the computing time increases linearly with the number of conformations and the quality of the result drops with larger differences between the most similar conformation of the ensemble and the actual complex conformation. Thus a balance must be struck between computing time requirements and the desire to cover all of conformational space. 

Since complexes 92 and 93 are achiral, it is likely that they form tactic polymers via a chain-end control process (vide infra). To increase the isospecificity of complex 93 for polymerization, Schrock replaced the achiral alkoxide groups with a range of Q-symmetric diols to create asymmetric complexes 94—98. These complexes, especially rac-95, exert an exceptionally high degree of stereochemical control in the polymerization of 90 and 91, producing polymers that are >99% cis and have >99% isotactic (mm) triads. Even complex 98 that employs a conformationally flexible ligand produces highly isotactic, cis polymers. 

Flexibility range The range of bite angles for which the calculated energy of a ligand increases by at most 3 kcalmol" ... 

Conformational Adjustments The conformations of protein and ligand in the free state may differ from those in the complex. The conformation in the complex may be different from the most stable conformation in solution, and/or a broader range of conformations may be sampled in solution than in the complex. In the former case, the required adjustment raises the energy, in the latter it lowers the entropy in either case this effect favors the dissociated state (although exceptional instances in which the flexibility increases as a result of complex formation seem possible). With current models based on two-body potentials (but not with force fields based on polarizable atoms, currently under development), separate intra-molecular energies of protein and ligand in the complex are, in fact, definable. However, it is impossible to assign separate entropies to the two parts of the complex. 

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