Design scoring schemes

Lin, J. H., Perryman, A. L., Schames, J. R., and McCammon, J. A. (2003) The relaxed complex method accommodating receptor flexibility for drug design with an improved scoring scheme. Biopolymers 68,47-62. 

The goal of the prioritization scheme is to design the scores so that the overall worst looking compounds are de-emphasized and the best looking compounds are moved toward the top of the list. Thus, it is important to ensure that the best and the worst compounds are clearly separated and that the vast bulk of the population is in the middle. The normal distribution is ideally suited for this and thus it is advantageous to transform our component scores into a normal-like distribution. Enterprise Miner from SAS Institute was used to do this as it has a maximize normality transformation built into it. 

Figure 22. Process of evaluation, scoring, and designation of the OPCW proficiency-testing scheme...

The process of evaluation, scoring, and designation of the OPCW proficiency-testing scheme is shown in Figure 22. The process is known to have three weaknesses, the areas of weakness are highlighted in Figure 22 and summarized in the following ... 

Fig. 3. MapMaker is a combinatorial library optimization tool developed at ArQule, currently used in the design of screening libraries. The system is represented as a black box, since the details of operation are hidden by a web interface, to which chemists provide a reaction scheme, lists of candidate reagents, and the number of reagents desired for each dimension of a library, and from which they retrieve lists of reagents that encode for the optimized library. Internally, MapMaker enumerates the full virtual array, calculates the desired properties and coordinates in chemical space for the virtual compounds, and performs the optimization using a genetic algorithm. Consensus scoring following property calculation allows the system to optimize around an arbitrary number of computed properties, which are determined at run-time.

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