Clustering biological responses

A method proposed for determining which molecular descriptors of a set of compounds are associated with a biological response. The active compounds are expected to be similar to each other with respect to these relevant descriptors and so will cluster together in the space defined by the corresponding descriptors. 

This approach, originally proposed for binary response variables [McFarland and Cans, 1986], was extended to the quantitative biological responses y, scaled between zero and one [Rose and Wood, 1998] and then called Generalized Cluster Significance Analysis (GCSA). 

FIGURE 12.7 Partial view of a Structure-Activity Analysis for cytidine (CID 596) and it 2-D similarity neighbors for all bioassays tested within PubChem, with compounds clustered by 2-D structure similarity and assays clustered based on compound biological response. 

Metallothioneins (MT) are unique 7-kDa proteins containing 20 cysteine molecules bounded to seven zinc atoms, which form two clusters with bridging or terminal cysteine thiolates. A main function of MT is to serve as a source for the distribution of zinc in cells, and this function is connected with the MT redox activity, which is responsible for the regulation of binding and release of zinc. It has been shown that the release of zinc is stimulated by MT oxidation in the reaction with glutathione disulfide or other biological disulfides [334]. MT redox properties led to a suggestion that MT may possesses antioxidant activity. The mechanism of MT antioxidant activity is of a special interest in connection with the possible antioxidant effects of zinc. (Zinc can be substituted in MT by some other metals such as copper or cadmium, but Ca MT and Cu MT exhibit manly prooxidant activity.)... 

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