Mode matches in hydrophobic free energy eigenfunctions predict peptide-protein interactions.
Mode matches in hydrophobic free energy eigenfunctions predict peptide-protein interactions.
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DOI：
10.1002/(sici)1097-0282(199808)46:2
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发表时间：
1998-08
期刊：
影响因子：
2.9
通讯作者：
A. Mandell;M. Owens;K. Selz;W. N. Morgan;M. Shlesinger;C. Nemeroff
中科院分区：
文献类型：
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作者：
A. Mandell;M. Owens;K. Selz;W. N. Morgan;M. Shlesinger;C. Nemeroff
利用正交分解氨基酸序列的自协方差矩阵确定神经降压素（NT）、胆囊收缩素（CCK）、人多巴胺D2受体[（DA）D2]和人多巴胺转运蛋白（DAT）的主要统计疏水自由能反频率氨基酸波长作为疏水模式，作为疏水自由能当量（kcal/mol）。首先将与特征值相关的特征向量与原始序列进行卷积，构造特征函数。利用离散三角小波变换和全极点、最大熵功率谱变换对特征函数进行了分析。这产生了占主导地位的疏水性自由能模式，其中大部分是否则失去了平滑的亲水性图或污染的端部效应和多模态在传统的傅立叶变换的干净的表示。NT与（DA）D2、CCK与DAT之间存在模式匹配，但匡威则不匹配。这些模式匹配成功地预测了NT-（DA）D2与CCK-（DA）D2在~ 3 H-螺哌隆与（DA）D2结合上的非线性动力学相互作用，以及在（DA）D2和DAT cDNA稳定转染的细胞系中，CCK-DAT而不是NT-DAT在[N-甲基-3H]-WIN 35，428与DAT结合上的非线性动力学相互作用。疏水自由能本征函数的主导模式的计算可能有助于预测功能相关的肽-膜蛋白相互作用，甚至跨神经递质家族。
The dominant statistical hydrophobic free energy inverse frequencies amino acid wavelengths as hydrophobic modes, of neurotensin (NT), cholescystokinin (CCK), the human dopamine D2 receptor [(DA)D2], and the human dopamine transporter (DAT) were determined using orthogonal decomposition of the autocovariance matrices of their amino acid sequences as hydrophobic free energy equivalents in kcal/mol. The leading eigenvalues-associated eigenvectors were convolved with the original series to construct eigenfunctions. Eigenfunctions were further analyzed using discrete trigonometric wavelet and all poles, maximum entropy power spectral transformations. This yielded clean representations of the dominant hydrophobic free energy modes, most of which are otherwise lost in the smoothing of hydropathy plots or contaminated by end effects and multimodality in conventional Fourier transformations. Mode matches were found between NT and (DA)D2 and between CCK and DAT, but not the converse. These mode matches successfully predicted the nonlinear kinetic interactions of NT-(DA)D2 in contrast with CCK-(DA) D2 on 3H-spiperone binding to (DA) D2, and by CCK-DAT but not NT-DAT on [N-methyl-3H]-WIN 35,428 binding to DAT in (DA)D2 and DAT cDNA stably transfected cell lines without known NT or CCK receptors. Computation of the dominant modes of hydrophobic free energy eigenfunctions may help predict functionally relevant peptide-membrane protein interactions, even across neurotransmitter families.