Sergeĭko A P, Stepanchikova A V, Sobolev B N, Zotchev S B, Lagunin A A, Filimonov D A, Poroĭkov V V
Biomed Khim. 2007 Sep-Oct;53(5):522-31.
We propose an approach to rational design of new polyketides with the required spectrum of biological activity. We developed BioGenPharm software for generation of polyketide combinatorial libraries, prediction of activity spectra for the generated structures and selection of molecules with the required properties on the basis of user defined input parameters and selection criteria. For prediction of polyketide activity spectra we used PASS algorithm (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 cutting points for probability of the presence of activity (Pa), which provide optimal combination of such parameters as sensitivity, specificity, concordance was considered. Applicability of the described method has been illustrated by generation of a virtual library of the erythromycin analogues and selection substances for which the probability of hepatotoxic action is low.
我们提出了一种合理设计具有所需生物活性谱的新型聚酮化合物的方法。我们开发了BioGenPharm软件，用于生成聚酮化合物组合文库、预测所生成结构的活性谱，并根据用户定义的输入参数和选择标准选择具有所需特性的分子。为了预测聚酮化合物的活性谱，我们使用了PASS算法（http://www.ibmc.msk.ru/PASS）。相对于包含来自《天然产物词典》的242种天然大环内酯的评估集，对PASS对聚酮化合物的预测能力进行了验证。平均预测准确率为75.5%。考虑了选择活性存在概率（Pa）的切点的问题，该切点可提供诸如敏感性、特异性、一致性等参数的最佳组合。通过生成红霉素类似物的虚拟文库以及选择肝毒性作用概率较低的物质，说明了所述方法的适用性。
