A Novel Subshape Molecular Descriptor

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• 作者：Santosh Putta ; John Eksterowicz ; Christian Lemmen ; and Robert Stanton
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2003
• 出版时间：September 2003
• 年：2003
• 卷：43
• 期：5
• 页码：1623 - 1635
• 全文大小：634K
• 年卷期：v.43,no.5(September 2003)
• ISSN：1549-960X

文摘

Molecules with similar shapes and features often have similar biological activity. Several computationalapproaches search chemical databases for new leads or templates based on overall molecular shape similarity.However, active molecules often present critical subshapes that are required for binding, which may bemissed by comparing overall shape similarity. We present a new approach to compare molecular shapes ofdifferent sizes and to calculate subshape similarity. We developed a skeletal representation of the shapewhich is topologically unrelated to covalent chemical connectivity. This simplifies rotational and translationalsampling. We test initial possible alignments by matching similar triangles. This triangle-matching filterrapidly eliminates most geometrically impossible matches. Surviving matches are filtered further in successivestages. These stages involve direction, feature, and shape matching procedures. Our approach is applied toseveral situations demonstrating lead discovery and evolution.