Predicting allosteric pockets in protein biological assemblages.
Predicting allosteric pockets in protein biological assemblages.
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DOI：
10.1093/bioinformatics/btad275
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发表时间：
2023-05-04
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--
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Allostery能够改变由结合诱导的蛋白质在远距离位置的动态行为。在这里，我们提出了APOP，一种新的变构口袋预测方法，它扰动的口袋中形成的结构，通过加强成对的相互作用在整个口袋的弹性网络，模拟配体结合。基于全局模式频率的变化以及它们的平均局部疏水性对口袋进行排名，当在由单体和多聚体组装组成的变构蛋白的数据集上进行测试时，导致高预测成功率。在104个测试案例中，APOP预测蛋白质中可用的多个口袋中的前3个排名内的92个已知变构口袋。此外，我们证明APOP也可以在蛋白质中找到新的替代变构口袋。特别有趣的发现是发现了以前被忽视的位于许多蛋白质生物聚集体中心的大口袋;在这些位点结合配体可能对改变蛋白质的全局动力学特别有效。APOP作为开源代码（https：//github.com/Ambuj-UF/APOP）和Web服务器（https://apop.bb.iastate.edu/）免费提供。
Allostery enables changes to the dynamic behavior of a protein at distant positions induced by binding. Here, we present APOP, a new allosteric pocket prediction method, which perturbs the pockets formed in the structure by stiffening pairwise interactions in the elastic network across the pocket, to emulate ligand binding. Ranking the pockets based on the shifts in the global mode frequencies, as well as their mean local hydrophobicities, leads to high prediction success when tested on a dataset of allosteric proteins, composed of both monomers and multimeric assemblages. Out of the 104 test cases, APOP predicts known allosteric pockets for 92 within the top 3 rank out of multiple pockets available in the protein. In addition, we demonstrate that APOP can also find new alternative allosteric pockets in proteins. Particularly interesting findings are the discovery of previously overlooked large pockets located in the centers of many protein biological assemblages; binding of ligands at these sites would likely be particularly effective in changing the protein’s global dynamics. APOP is freely available as an open-source code (https://github.com/Ambuj-UF/APOP) and as a web server at https://apop.bb.iastate.edu/.
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影响因子：
16.6
作者：
Amor, B. R. C.;Schaub, M. T.;Yaliraki, S. N.;Barahona, M.
通讯作者：
Barahona, M.
影响因子：
4.8
作者：
Cho, Y;Sharma, V;Sacchettini, JC
通讯作者：
Sacchettini, JC
DOI：
10.1016/s1359-0278(97)00024-2
发表时间：
1997-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
Bahar, I;Atilgan, AR;Erman, B
通讯作者：
Erman, B
丙酮酸激酶M2激活剂促进四聚体形成并抑制肿瘤发生。
影响因子：
14.8
作者：
Anastasiou, Dimitrios;Yu, Yimin;Israelsen, William J.;Jiang, Jian-Kang;Boxer, Matthew B.;Hong, Bum Soo;Tempel, Wolfram;Dimov, Svetoslav;Shen, Min;Jha, Abhishek;Yang, Hua;Mattaini, Katherine R.;Metallo, Christian M.;Fiske, Brian P.;Courtney, Kevin D.;Malstrom, Scott;Khan, Tahsin M.;Kung, Charles;Skoumbourdis, Amanda P.;Veith, Henrike;Southall, Noel;Walsh, Martin J.;Brimacombe, Kyle R.;Leister, William;Lunt, Sophia Y.;Johnson, Zachary R.;Yen, Katharine E.;Kunii, Kaiko;Davidson, Shawn M.;Christofk, Heather R.;Austin, Christopher P.;Inglese, James;Harris, Marian H.;Asara, John M.;Stephanopoulos, Gregory;Salituro, Francesco G.;Jin, Shengfang;Dang, Lenny;Auld, Douglas S.;Park, Hee-Won;Cantley, Lewis C.;Thomas, Craig J.;Heiden, Matthew G. Vander
通讯作者：
Heiden, Matthew G. Vander
影响因子：
3.7
作者：
Mishra SK;Jernigan RL
通讯作者：
Jernigan RL