Development of Scoring Functions

The major challenges to be overcome in the further development of scoring functions include... 

This methodology has been used to predict the structure of loops of helical-bundle proteins, given the positions of the connection to the helices (372). Because of the uncertainties in secondary structure predictions that are used as inputs to constrain the search, any single prediction of the method must be viewed with skepticism. Development of scoring functions that discriminate between alternative models at the Ca level of resolution would complement this approach. 

In addition, there have also been a number of efforts to find more efficient ways to categorise and enumerate compounds. One approach to defining the relationship of compounds to each other uses a chemical space defined by a set of 500 compounds described with 60 molecular descriptors onto which novel compounds can then be mapped.116 Another approach that has been described uses a rule-based classification scheme to define the common scaffold or core of compounds.117 This approach has been taken further to develop a scoring function to allow the prioritisation of compound libraries for testing.118... 

There are several approaches to address the issue of scoring and to improve the performance of scoring functions in terms of pose prediction and affinity correlation. A selection of recent developments is discussed in the next section. 

The estimation of potency was found to be greatly improved upon minimization of the generated structures. Rather than derive a relationship for a specific protein and its ligands, Bohm has developed a scoring function that takes into account various interactions and is derived from a linear regre.ssion analysis of 45 protein-ligand complexes containing 24 different protein families " ... 

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