Heil Burkhard, Ludwig Jost, Lichtenberg-Fraté Hella, Lengauer Thomas
Universität Bonn, IZMB Kirschallee 1, 53115 Bonn, Germany.
Bioinformatics. 2006 Jul 1;22(13):1562-8. doi: 10.1093/bioinformatics/btl132. Epub 2006 Apr 4.
Potassium channels are mainly known for their role in regulating and maintaining the membrane potential. Since this is one of the key mechanisms of signal transduction, malfunction of these potassium channels leads to a wide variety of severe diseases. Thus potassium channels are priority targets of research for new drugs, despite the fact that this protein family is highly variable and closely related to other channels, which makes it very difficult to identify new types of potassium channel sequences.
Here we present a new method for identifying potassium channel sequences (PSM, Property Signature Method), which-in contrast to the known methods for protein classification-is directly based on physicochemical properties of amino acids rather than on the amino acids themselves. A signature for the pore region including the selectivity filter has been created, representing the most common physicochemical properties of known potassium channels. This string enables genome-wide screening for sequences with similar features despite a very low degree of amino acid similarity within a protein family.
钾通道主要因其在调节和维持膜电位方面的作用而闻名。由于这是信号转导的关键机制之一,这些钾通道的功能异常会导致多种严重疾病。因此,尽管该蛋白家族高度可变且与其他通道密切相关,使得识别新型钾通道序列非常困难,但钾通道仍是新药研究的优先靶点。
在此,我们提出了一种识别钾通道序列的新方法(PSM,特性签名法),与已知的蛋白质分类方法不同,该方法直接基于氨基酸的物理化学性质而非氨基酸本身。已经创建了包括选择性过滤器在内的孔区域的签名,代表了已知钾通道最常见的物理化学性质。尽管蛋白质家族内氨基酸相似性程度很低,但这个字符串能够在全基因组范围内筛选具有相似特征的序列。