PinaColada: peptide-inhibitor ant colony ad-hoc design algorithm
PinaColada: peptide-inhibitor ant colony ad-hoc design algorithm
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DOI：
10.1093/bioinformatics/btw133
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发表时间：
2016-08-01
期刊：
影响因子：
5.8
通讯作者：
Wolfson, Haim J.
中科院分区：
文献类型：
--
作者：
Zaidman, Daniel;Wolfson, Haim J.
动机：蛋白质-蛋白质相互作用（PPI）抑制剂的设计是结构生物信息学的主要挑战。肽，特别是短肽（5-15个氨基酸长），是抑制蛋白-蛋白复合物的天然候选者，因为它具有几个吸引人的特性，如与蛋白质结合位点的高结构相容性（模仿蛋白质的表面）、小尺寸以及与蛋白质表面形成强热点结合连接的能力。高效合理的肽设计仍然是计算机辅助药物设计的主要挑战，因为可能的序列空间巨大，肽长度呈指数级增长，肽构象具有高度的灵活性。结果：在本文中，我们提出了一种新的计算方法PinaColada，用于设计蛋白质-蛋白质相互作用的肽抑制剂。我们采用一种蚁群优化启发式算法，用于探索长度为n的肽序列的指数空间（20n），并结合我们的快速机器人驱动的PepCrawler算法，探索每个候选序列的构象空间。PinaColada在一台戴尔PowerEdge 2.8GHZ、20核、256GB内存的计算机上并行运行，设计一个5-15个氨基酸长度的肽需要24小时。可用性和实现：一个在线服务器可在：http://bioinfo3d.cs.tau.ac.il/PinaColada/。
Motivation: Design of protein-protein interaction (PPI) inhibitors is a major challenge in Structural Bioinformatics. Peptides, especially short ones (5-15 amino acid long), are natural candidates for inhibition of protein-protein complexes due to several attractive features such as high structural compatibility with the protein binding site (mimicking the surface of one of the proteins), small size and the ability to form strong hotspot binding connections with the protein surface. Efficient rational peptide design is still a major challenge in computer aided drug design, due to the huge space of possible sequences, which is exponential in the length of the peptide, and the high flexibility of peptide conformations.Results: In this article we present PinaColada, a novel computational method for the design of peptide inhibitors for protein-protein interactions. We employ a version of the ant colony optimization heuristic, which is used to explore the exponential space (20n) of length n peptide sequences, in combination with our fast robotics motivated PepCrawler algorithm, which explores the conformational space for each candidate sequence. PinaColada is being run in parallel, on a DELL PowerEdge 2.8GHZ computer with 20 cores and 256GB memory, and takes up to 24 h to design a peptide of 5-15 amino acids length.Availability and implementation: An online server available at: http://bioinfo3d.cs.tau.ac.il/PinaColada/.