Target-specific optimization method

The target-specific optimization method (TOP) by Seifert focuses entirely on discrimination between actives and decoys [148]. Enrichment factors were shown to be insufficient to evaluate the discrimination properties of a scoring function. 

Notwithstanding, inhalation cannot be considered an optimal method for the delivery of CO for several reasons [20]. In practical terms, it is restricted to hospital settings due to its complexity and potential dangers. On a more fundamental basis, however, distribution of CO through circulation does not discriminate between healthy and diseased tissues. This lack of tissue specificity is particularly serious for a drug like CO, which may target heme proteins in every possible tissue, and is exactly the opposite of the natural way in which HO effects its protective action increase the local concentration of CO at the site of disease via inducible HO-1 expression [6,7]. 

Introduction of isotopes by exchange (direct replacement) is the most straightforward method of preparation of labeled targets from their unlabeled analogs. This approach is used mainly in tritium chemistry, where its advantage of simplicity is, however, offset by wide variation in (and sometimes by the unpredictability of) the extent and position of labeling. Therefore substrate-specific optimization might be... 

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