Using Molecular Mechanics Methods

You can use any ab initio SCF calculation and all the semi-empiri-cal methods, except Extended Hiickel, for molecular dynamics simulations. The procedures and considerations are similar for simulations using molecular mechanics methods (see Molecular Dynamics on page 69). 

The naturally occurring ligand enterobactin (Fig. 12.5) is one of the most efficient binders of iron(III). It forms complexes which have strictly right-handed chirality and the reasons for this have been analyzed using molecular mechanics methods, as have the reasons for the superiority of enterobactin as an iron-binding ligandl2,7]. 

Hindered rotation about the P-C bonds in phosphine ligands can also produce conformational isomers and DNMR spectra below room temperature.There have been moderately successful attempts to estimate relative conformational stability using molecular mechanics methods with force fields adjusted for metal compounds.These different conformations can produce conformational isomers that are diastereomers in complexes with chiral metal centers, such as in (39) and (40). Propeller chirality, which is designated as P and M, has also been studied in triphenylsilane and triphenylstannane. ... 

Finally, it must be noted that the conformational behavior characteristic of the exo anomeric effect could be reproduced not only by MO calculations but also using molecular mechanics methods, as was shown by Navio and Molina (105) for twelve 2-alkoxytetrahydropyran derivatives 38 (Figure 6) (see Section III.A.6). 

Approaches related to overcoming these limitations will be discussed in the context of the examples presented ahead. Furthermore, when using molecular mechanics methods, the modeling of electronic effects is not usually addressed specifically. This can lead to additional uncertainties in terms of the computed structures and conformer distributions. 

Another related computational approach to ligand discovery is the method of database mining. Here, the HTS approach is essentially carried out in-silico. Libraries of small molecules are converted to three-dimensional structures using molecular mechanics methods incorporated into programs such as CONCORD and GORINA.These three-dimensional libraries of small molecules can. in theory, contain almost infinite numbers of potential ligands. In practice, it is convenient to consider compounds that are already (commercially) available. The Available Chemicals Database (ACD), - for example, contains some 260,000 compounds and is frequently used as the basis for database mining trials. 

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