蛋白质亚硝基化修饰位点预测工具 —— GPS-SNO 1.0

ゞ浴缸里的玫瑰 2022-05-14 22:53 494阅读 0赞

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   <td> <a href="http://www.plosone.org/home.action" rel="nofollow"><img src="http://sno.biocuckoo.org/images/coverimage.jpeg" alt="plosone" width="107" height="87"></a> </td> 
   <td> <p><strong>GPS-SNO: Computational prediction of protein <em>S</em> -nitrosylation sites with a modified GPS algorithm. </strong> <a href="mailto:xueyu@mail.hust.edu.cn" rel="nofollow">Yu Xue</a> , Zexian Liu, Xinjiao Gao, Changjiang Jin, Longping Wen, Xuebiao Yao, and <a href="mailto:renjian@ustc.edu.cn" rel="nofollow">Jian Ren</a> . <strong>Plos One</strong> . 2010;5(6):e11290 <a href="http://www.plosone.org/article/info%3Adoi/10.1371/journal.pone.0011290" rel="nofollow">[Full Text]</a> <a href="http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi/10.1371/journal.pone.0011290&amp;representation=PDF" rel="nofollow">[PDF]</a> </p> </td> 
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The 1998 Nobel Prize in Physiology or Medicine was awarded for seminal discoveries that **[nitric oxide (NO) ][nitric oxide _NO_]** is a freely-diffusible signalling molecule and second messenger, regulates the production of cyclic GMP (cGMP), and plays essential roles in the cardiovascular system. Later, flood of studies challenged this fundamental view by observing that NO could spatially and temporally target specific cysteine thiols and transition metals of proteins, a reversibly post-translational modification (PTM) termed as [***S* \-nitrosylation** ][S_ _-nitrosylation_] ([Foster, *et al* ., 2009][Foster_ _et al_ ._ 2009] ; [Foster, *et al* ., 2003][Foster_ _et al_ ._ 2003] ; [Hess, *et al* ., 2005][Hess_ _et al_ ._ 2005] ; [Hess, *et al* ., 2001][Hess_ _et al_ ._ 2001] ; [Stamler, *et al* ., 2001][Stamler_ _et al_ ._ 2001] ; [Tannenbaum and White, 2006][Tannenbaum and White_ 2006] ). Although enzymatic mechanisms of protein *S* \-nitrosylation were still elusive, several enzymes were proven to facilitate *S* \-nitrosylation or de-nitrosylation reactions. For example, Cu, Zn superoxide dismutase (SOD) and thioredoxin (TRX) could promote *S* \-nitrosylation, while protein disulfide isomerase (PDI) might regulate de-nitrosylation ([Hess, *et al* ., 2005][Hess_ _et al_ ._ 2005] ; [Tannenbaum and White, 2006][Tannenbaum and White_ 2006] ). Current progresses proposed that *S* \-nitrosylation could modulate proteins' stabilities ([Li, *et al* ., 2007][Li_ _et al_ ._ 2007] ), activities ([Tsang, *et al* ., 2009][Tsang_ _et al_ ._ 2009] ) and trafficking ([Hernlund, *et al* ., 2009][Hernlund_ _et al_ ._ 2009] ; [Ozawa, *et al* ., 2008][Ozawa_ _et al_ ._ 2008] ), and play important roles in a variety of biological processes, including transcriptional regulation ([Li, *et al* ., 2007][Li_ _et al_ ._ 2007] ), cell signalling ([Whalen, *et al* ., 2007][Whalen_ _et al_ ._ 2007] ), apoptosis ([Tsang, *et al* ., 2009][Tsang_ _et al_ ._ 2009] ), chromatin remodeling ([Nott, *et al* ., 2008][Nott_ _et al_ ._ 2008] ) and so on. Moreover, aberrant *S* \-nitrosylation has been implicated in numerous diseases and cancers ([Foster, *et al* ., 2009][Foster_ _et al_ ._ 2009] ; [Foster, *et al* ., 2003][Foster_ _et al_ ._ 2003] ; [Tsang, *et al* ., 2009][Tsang_ _et al_ ._ 2009] ). In this regard, experimental identification of *S* \-nitrosylated proteins with their sites will be a foundation of understanding the molecular mechanisms and regulatory roles of *S* \-nitrosylation.

In this work, we manually collected **467** experimentally verified *S* \-nitrosylation sites in **302** unique proteins from scientific literature. Previously, we developed an algorithm of **[GPS 2.0][]** (Group-based Prediction System) for prediction of kinase-specific phosphorylation sites ([Xue, *et al* ., 2008][Xue_ _et al_ ._ 2008] ). Here, we greatly improved the method and released **GPS 3.0** algorithm. Then we developed a novel computational software of **GPS-SNO 1.0** for prediction of *S* \-nitrosylation sites. The leave-one-out validation and 4-, 6-, 8-, 10-fold cross-validations were calculated to evaluate the prediction performance and system robustness. By comparison, the performance of GPS 3.0 algorithm was much better than several other approaches, with an accuracy of 75.70%, a sensitivity of 55.32% and a specificity of 80.11% under the low threshold. As applications of GPS-SNO 1.0, we also collected 485 potentially *S* \-nitrosylated substrates from PubMed. These proteins were detected from large-scale or small-scale studies, while the exact *S* \-nitrosylation sites were still not experimentally determined. Successfully, we predicted 371 (~76%) of these targets with at lease one potential *S* \-nitrosylation site. These prediction results might be a useful reservoir for further experimental verification. Finally, the online service and local packages of GPS-SNO 1.0 were implemented in JAVA 1.4.2 and freely available at: [**http://sno.biocuckoo.org/** ][http_sno.biocuckoo.org_] .

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***GPS-SNO 1.0 User Interface***

[bg06.gif]: http://sno.biocuckoo.org/images/bg06.gif
[nitric oxide _NO_]: http://en.wikipedia.org/wiki/Nitric_oxide
[S_ _-nitrosylation_]: http://en.wikipedia.org/wiki/Nitrosylation
[Foster_ _et al_ ._ 2009]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19726230
[Foster_ _et al_ ._ 2003]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12727142
[Hess_ _et al_ ._ 2005]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15688001
[Hess_ _et al_ ._ 2001]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11175760
[Stamler_ _et al_ ._ 2001]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11572774
[Tannenbaum and White_ 2006]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17168564
[Li_ _et al_ ._ 2007]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17434127
[Tsang_ _et al_ ._ 2009]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19273858
[Hernlund_ _et al_ ._ 2009]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19328230
[Ozawa_ _et al_ ._ 2008]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18691971
[Whalen_ _et al_ ._ 2007]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17482545
[Nott_ _et al_ ._ 2008]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18754010
[GPS 2.0]: http://gps.biocuckoo.org/
[Xue_ _et al_ ._ 2008]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18463090%20
[http_sno.biocuckoo.org_]: http://sno.biocuckoo.org/
[GPS-SNO.gif]: /images/20220515/18fd63f346594eabbc998e1057d86e1a.png