A COMPUTER-AIDED THERMODYNAMIC APPROACH FOR PREDICTING THE FORMATION OF Z-DNA IN NATURALLY-OCCURRING SEQUENCES

A COMPUTER-AIDED THERMODYNAMIC APPROACH FOR PREDICTING THE FORMATION OF Z-DNA IN NATURALLY-OCCURRING SEQUENCES
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DOI:
10.1002/j.1460-2075.1986.tb04558.x
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发表时间:
1986-10-01
期刊:
影响因子:
11.4
通讯作者:
RICH, A
RICH, A
中科院分区:
生物学1区
文献类型:
--
作者:
HO, PS;ELLISON, MJ;RICH, A

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一个特定的DNA片段采用左手Z-构象的容易程度在很大程度上取决于序列和它所经历的负超螺旋的程度。我们描述了一个计算机程序(Z-hunt),该程序旨在搜索天然存在的DNA的长序列,并检索长度高达24 bp的核苷酸组合,这些核苷酸组合显示出强烈的Z-DNA形成倾向。Z-hunt中包含一个统计力学模型,该模型基于迄今为止积累的B到Z转变的经验确定的能量参数。序列的Z-形成潜力通过将其行为作为负超螺旋度的函数相对于从超过80,000个组合组装的类似大小的随机生成的核苷酸序列的行为进行排名来评估。该程序使得直接比较具有不同碱基组成和不同序列长度的序列的Z形成潜力成为可能。使用Z-hunt,我们分析了噬菌体phi X174、质粒pBR 322、动物病毒SV 40和真核腺病毒2的复制形式的DNA序列。这些结果与其他人先前从实验中获得的结果进行了比较,这些实验旨在使用对左手DNA构象具有特异性的探针定位这些序列中的Z-DNA形成区域。
The ease with which a particular DNA segment adopts the left‐handed Z‐conformation depends largely on the sequence and on the degree of negative supercoiling to which it is subjected. We describe a computer program (Z‐hunt) that is designed to search long sequences of naturally occurring DNA and retrieve those nucleotide combinations of up to 24 bp in length which show a strong propensity for Z‐DNA formation. Incorporated into Z‐hunt is a statistical mechanical model based on empirically determined energetic parameters for the B to Z transition accumulated to date. The Z‐forming potential of a sequence is assessed by ranking its behavior as a function of negative superhelicity relative to the behavior of similar sized randomly generated nucleotide sequences assembled from over 80,000 combinations. The program makes it possible to compare directly the Z‐forming potential of sequences with different base compositions and different sequence lengths. Using Z‐hunt, we have analyzed the DNA sequences of the bacteriophage phi X174, plasmid pBR322, the animal virus SV40 and the replicative form of the eukaryotic adenovirus‐2. The results are compared with those previously obtained by others from experiments designed to locate Z‐DNA forming regions in these sequences using probes which show specificity for the left‐handed DNA conformation.