文章基本信息

标题：Exploring Unique Structures: Flexibility is a Significant Factor in Biological Activity
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作者：Kazuto Ohkura
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：6
页码：1025-1036
DOI：10.1248/bpb.30.1025
出版社：The Pharmaceutical Society of Japan
摘要：The effect of molecular flexibility on biological activity was described for soft ( e.g. hGH peptides) and hard molecules ( e.g. biscoclaurine-type alkaloids). These molecules had a macrocyclic structure during molecular mechanics analysis, and the minimum essential unit, which affects insulin-involved fatty acid synthesis, was observed. The flexibility of the molecular center is concerning with biological activity through the diversification of structural feature, and compared with two types of molecules which have a rigid (haloacetylcarbamoyl-2-nitroimidazole analogs: chiral-TXs) or flexible (bis-quaternary ammonium compounds: bis-QACs) molecular center. Center flexibility reflected the conformation occurrence in TXs and bis-QACs. A parameter (solvation-free energy: dGW), which reflects structural hydrophobicity, was shown, and applied to the molecular design of brefeldin A analog. This hydrophobic index was very useful, and was used for conformational analysis of chiral-TXs and bis-QACs. In molecular dynamics analysis of cholesterol-dependent cytolysin ( e.g. storeptolysin O) and -independent cytolysin ( e.g. intermedilysin), whole molecules moved like a bow and different conformations were shown in every moment. In such situations, the membrane-associated 11mer region in these cytolysins were flexible and could always interact with extramolecular factors ( e.g. membrane constitution).
关键词：molecular flexibility;molecular dynamics;essential unit