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首页> 外文期刊>BMC Genomics >Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets
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Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets

机译：与空间有关的药物基序，可快速搜索蛋白质结合基序和多药理学靶标

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Background To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. Results We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://?gemdock.?life.?nctu.?edu.?tw/?SRP/? . Conclusions SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery.
机译：背景技术发现抑制多种蛋白质的化合物（即多药理学靶标）是复杂疾病（例如癌症和糖尿病）的新范例。通常，多药理蛋白通常共享相似的局部结合环境和基序。随着蛋白质结构数量的指数增长，寻找相似的结构结合基序（药物基序）是药物发现（例如副作用和旧药物的新用途）和蛋白质功能的一项紧迫任务。结果我们开发了一种与空间有关的药物基序（称为SRPmotif）方法，可以通过搜索蛋白质结构数据库来识别结合基序。 SRPmotif能够识别包含空间不连续的药物基序的保守结合环境，这些空间不连续的药物基序通常是具有蛋白质功能特定理化性质的短保守肽。在356种药物基序中，有56.5％的相互作用残基是高度保守的。实验结果表明，基于基因本体论（GO），每种蛋白质-配体复合物的81.1％和92.7％的多药理学目标分别用相同的生物过程（BP）和分子功能（MF）术语标注。我们的实验结果表明，鉴定出的药物基序通常由功能（活性）位点中的关键残基组成，并在蛋白质功能中发挥关键作用。 SRPmotif可从http：//？gemdock。？life。？nctu。？edu。？tw /？SRP /？获得。 。结论SRPmotif能够通过快速搜索蛋白质结构数据库来鉴定相似的药理接口和共享相似的多药理学靶标结合环境的药基。药物基序描述了用于药物发现和蛋白质功能的结合环境的保守性。此外，这些药物基序为发现新的基于序列的基序以从蛋白质序列数据库预测蛋白质功能提供了线索。我们认为SRPmotif可用于阐明蛋白质功能和药物发现。

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