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Molecules 2010, 15, 5031-5044; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Selecting Diversified Compounds to Build a Tangible Library for Biological and Biochemical Assays Qiong Gu, Jun Xu * and Lianquan Gu * Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle at University City, Guangzhou, 510006, China * Authors to whom correspondence should be addressed; E-Mails: xujun9@ (J.X.); cedc42@ (L.Q.G.). Received: 2 July 2010; in revised form: 14 July 2010 / Accepted: 19 July 2010 / Published: 23 July 2010 Abstract: The quality of diverse compound selection mainly depends on cluster algorithms, descriptors, the combinations of the descriptors, and similarity metrics. The Jarvis-Patrick algorithm, MDL search keys, and Daylight fingerprints are a well accepted algorithm and structure descriptors for compound library diversity analysis. Based upon our 288 experiments on selecting compounds from various descriptor combinations, we have found (1) hybrid Daylight and MDL structural descriptors for diversity analyses can produce worse results; (2) selections based purely on 2,048-bit Daylight fingerprints yield better results than the ones based purely on MDL 166-bit search keys; (3) when Daylight fingerprints and MDL search keys are combined, it is better to compute the similarities independently, then to take the