Singular value decomposition of torsional angles of analogs of the dopamine reuptake inhibitor GBR 12909.
Singular value decomposition of torsional angles of analogs of the dopamine reuptake inhibitor GBR 12909.
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多巴胺再摄取抑制剂 GBR 12909 类似物扭转角的奇异值分解。
DOI：
10.1002/jcc.20371
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Venanzi,CarolA
中科院分区：
文献类型：
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作者：
Fiorentino,Anna;Pandit,Deepangi;Gilbert,KathleenM;Misra,Milind;Dios,Rose;Venanzi,CarolA
对大而灵活的分子，如多巴胺再摄取抑制剂GBR 12909(1)的分析是复杂的，因为它们可以具有广泛的密切相关的构象。分析的第一步是对构象进行分组。本文利用奇异值分解（SVD）对GBR 12909类似物的非环扭角相似性进行分组。本工作的意义在于，SVD首次应用于分析非常灵活的分子，它开发了一种新的圆形数据缩放技术，并使用一种独立于分子排列的技术对分子构象进行分组。研究了哌嗪(2)和哌啶(3)类似物1的700多个构象。分数和加载图分析表明，2的构象由于分子萘侧的扭转角而分成3个大基团，而3的构象由于分子双苯基侧的扭转角而分成9个基团。这些差异是由于2的未质子化哌嗪基氮上的氮反转，这导致了与3的构象集合不同的构象集合，而在相应的哌嗪基碳上不可能发生反转。©2006 Wiley期刊公司[J] .计算机工程学报，2006,31 (2):559 - 567
Analysis of large, flexible molecules, such as the dopamine reuptake inhibitor GBR 12909 (1), is complicated by the fact that they can take on a wide range of closely related conformations. The first step in the analysis is to classify the conformers into groups. Here, Singular Value Decomposition (SVD) was used to group conformations of GBR 12909 analogs by the similarity of their nonring torsional angles. The significance of the present work, the first application of SVD to the analysis of very flexible molecules, lies in the development of a novel scaling technique for circular data and in the grouping of molecular conformations using a technique that is independent of molecular alignment. Over 700 conformers each of a piperazine (2) and piperidine (3) analog of1were studied. Analysis of the score and loading plots showed that the conformers of2separate into three large groups due to torsional angles on the naphthalene side of the molecule, whereas those of3separate into nine groups due to torsional angles on the bisphenyl side of the molecule. These differences are due to nitrogen inversion at the unprotonated piperazinyl nitrogen of2, which results in a different ensemble of conformers than those of3, where no inversion is possible at the corresponding piperidinyl carbon. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 609–620, 2006