Computer-aided design of polyketides with the required properties

A. P. Sergeyko, A. V. Stepanchikova, B. N. Sobolev, S. B. Zotchev, A. A. Lagunin, D. A. Filimonov, V. V. Poroikov

    Publications: Contribution to journalArticlePeer Reviewed

    Abstract

    An approach to rational design of new polyketides with the required spectrum of biological activity has been proposed. We have developed the BioGenPharm software, which generates combinatorial libraries of polyketides based on the user-defined input parameters, performs prediction of biological activity spectra for the generated structures and selection of molecuels with the required properties. PASS algorithm has been applied for prediction of polyketide activity spectra (http://www.ibmc.msk.ru/PASS). Validation of PASS prediction ability for polyketides was performed vs. the evaluation set containing 242 natural macrolides from the Dictionary of Natural Products. The mean prediction accuracy was 75.5%. The problem of choice of the cutting points for probability of the presence of activity (Pa), which provides optimal combination of such parameters as sensitivity, specificity, concordance has been considered. Applicability of the described method has been illustrated by generation of a virtual library of the erythromycin analogues and selection of substances with low probability of the hepatotoxic effect.

    Original languageEnglish
    Pages (from-to)55-62
    Number of pages8
    JournalBiochemistry (Moscow) Supplement Series B: Biomedical Chemistry
    Volume2
    Issue number1
    DOIs
    Publication statusPublished - Mar 2008

    Austrian Fields of Science 2012

    • 301204 Pharmacognosy
    • 102004 Bioinformatics

    Keywords

    • Biological activity prediction
    • Macrolides
    • Polyketide synthase
    • Polyketides
    • Selection of substances with required properties
    • Virtuallibrary

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