The Martin paper[1] discussed whether similarity of chemical structures could implicate similarity of biological activities. The paper first discussed their findings in previous research led to their conclusion that when designing diverse combinatorial libraries, they would not considering compound that is gt;= 0.85 similar to a compound in their collection. However, other studies had results contradicts it. In this study, the authors used different methods to demonstrate how frequently molecules similar in structure have similar biological activities, and whether they should revise their previous conclusions. They used an IC50 dataset and the MAO dataset to quantify the fraction of chemicals with similar biological activities when they were similar. In their study, they have considered bias in their data, such as not including all active compounds, number of bits in fingerprints. The results showed that at gt;=0.85 Tanimoto similarity in Daylight fingerprints, only 30% of compounds similar to an active compound are active. They came to the conclusion that a redesign of strategies for compound acquisition: not all compounds that have a similarity over 0.85 should be excluded. Small portion of them should be included in the libraries. This paper reviewed many related researches, and clearly demonstrated the prefect results cannot be expected with the statistical nature of library design. However, it doesn’t quantify their suggestions of how much percent of the compounds with gt;=0.85 similarity should be considered and how they should be selected.br/br/1. Martin, Y.C. et al, “Do Structurally Similar Molecules Have Similar Biological Activity?”, iJ. Med. Chem./i, b2002/b, i45/i, 4350-4358

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