Field-based methods

A flow injection system with a micro-column of strong anion exchanger has been interfaced with an ICP-mass spectrometer via a microconeentrie nebulizer to perform on-line separation and trace determination of bromate in drinking waters (Elwaer, 1999 Elwaer et al, 2000). Method development studies examined the effect of sample injection volume, carrier stream flow rate and eluent concentration on system response. B asic performance data for this method were limit of detection, 0.13 ag/L (500 p-L sample injection) analysis time, 5 minutes per sample precision, 2.6%RSD (at5 g/L). 

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D similarity search methods are quite well developed. Thus, methods which attempt to find overlapping parts (atoms and functional groups) of the molecular moieties studied were reported first [31]. As discussed above for the case of 2D searching, these methods are of combinatorial complexity. To reduce this complexity some field-based methods have been introduced. In this case, the overlap of the fields of two structures is considered as a similarity measure. 

DG was primarily developed as a mathematical tool for obtaining spahal structures when pairwise distance information is given [118]. The DG method does not use any classical force fields. Thus, the conformational energy of a molecule is neglected and all 3D structures which are compatible with the distance restraints are presented. Nowadays, it is often used in the determination of 3D structures of small and medium-sized organic molecules. Gompared to force field-based methods, DG is a fast computational technique in order to scan the global conformational space. To get optimized structures, DG mostly has to be followed by various molecular dynamic simulation. 

Field-based methods generally utilize linear combinations of appropriate functions that are associated in some way with the atoms of the molecule under study ... 

A general workflow for the generation of pharmacophores from multiple ligands is outlined in Fig. 2.1. The field-based methods, although important and worth mentioning in this chapter, will be treated here separately from the classical pharmacophore modeling as defined above. 

Three main classes of fast scoring functions can be distinguished force field-based methods, empirical scoring functions, and knowledge-based methods. The following sections are dedicated to a separate discussion of each method. 

Force Field-Based Methods. An obvious idea to circumvent parameterization efforts for scoring is to use nonbonded energies of existing, well-established molecular mechanics force fields for the estimation of bind-... 

Field-based methods Laboratory-based Methods... 

However, the free energy of binding is a state function so, in a strict physical sense, additivity is not allowed. These scoring functions at low computational cost are suitable for the calculation of an estimation of the binding free energy. Three main classes can be separated force field-based methods, empirical methods, and knowledge-based methods. 

Note that these steps are equivalent to the force field-based method, but the forces are derived quantum mechanically. Accordingly, one can carry out simulations in the ground or electronically excited states as well as account for chemical reactions. 

Some recent approaches have involved using combinations of 2D and 3D descriptors. For example, BCUT descriptors have been used in combination with four-point pharmacophores [50], and field-based methods have been combined with 2D Daylight fingerprints [47],... 

Both quantum mechanical and force field-based methods have been employed in the attempt to model hydrogen transfer reactions. In free-radical chemistry, by far the most significant hydrogen transfer process involves the reaction between a carbon-centered radical and a chain-carrying reagent such as tributyltin hydride... 

Although the presented results do not offer the possibility to predict antimalarial potency in a quantitative manner, this method apparently allows an efficient discrimination between active and inactive analogues. Moreover, it takes into account aspects of charge delocalization which are difficult to capture by means of force-field based methods such as CoMFA. In view of the time and cost involved in such calculations, however, the authors propose this computationally more sophisticated method as a second selection step which could best be used after having sorted out the more active from the less active candidates by a less expensive 3D-QSAR modelling technique [110]. 

These are not the only molecular field based methods quite a large number of other variants have been developed " but there isn t space here to discuss them. There is one new development, however, which is qualitatively different to these approaches and that is a system called ParaSurf, which... 

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