SDM--a server for predicting effects of mutations on protein stability and malfunction.
SDM--a server for predicting effects of mutations on protein stability and malfunction.
复制标题
DOI：
10.1093/nar/gkr363
复制
发表时间：
2011-07
影响因子：
14.9
通讯作者：
Blundell TL
中科院分区：
文献类型：
--
作者：
Worth CL;Preissner R;Blundell TL
近年来，人类基因组计划、HapMap计划和全基因组关联研究等项目产生了大量的非同义单核苷酸多态性，这意味着不可能通过实验来表征基因产物上的所有突变，即阐明突变对蛋白质结构和功能的影响。然而，能够预测突变影响的自动方法将允许研究一组减少的突变。位点定向突变（Site Directed Mutator， SDM）是一种统计势能函数，它使用同源蛋白家族中环境特异性氨基酸取代频率来计算稳定性评分，这类似于野生型和突变型蛋白之间的自由能差。在这里，我们为SDM提供了一个web服务器（http://www-cryst.bioc.cam.ac.uk/~sdm/sdm.php），自2008年4月上线以来，已经收到了1万多份提交。要运行SDM，用户必须上传一个野生型结构以及突变的位置和氨基酸类型。返回的结果包括野生型和突变体残基的局部结构环境信息、稳定性评分预测和疾病关联预测。此外，野生型和突变型结构显示在Jmol applet中，并突出显示相关残基。
The sheer volume of non-synonymous single nucleotide polymorphisms that have been generated in recent years from projects such as the Human Genome Project, the HapMap Project and Genome-Wide Association Studies means that it is not possible to characterize all mutations experimentally on the gene products, i.e. elucidate the effects of mutations on protein structure and function. However, automatic methods that can predict the effects of mutations will allow a reduced set of mutations to be studied. Site Directed Mutator (SDM) is a statistical potential energy function that uses environment-specific amino-acid substitution frequencies within homologous protein families to calculate a stability score, which is analogous to the free energy difference between the wild-type and mutant protein. Here, we present a web server for SDM (http://www-cryst.bioc.cam.ac.uk/~sdm/sdm.php), which has obtained more than 10 000 submissions since being online in April 2008. To run SDM, users must upload a wild-type structure and the position and amino acid type of the mutation. The results returned include information about the local structural environment of the wild-type and mutant residues, a stability score prediction and prediction of disease association. Additionally, the wild-type and mutant structures are displayed in a Jmol applet with the relevant residues highlighted.
登录
查看更多内容
DOI：
10.1046/j.1432-1327.1998.2570001.x
发表时间：
1998-10-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bjorgo, E;Knappskog, PM;Flatmark, T
通讯作者：
Flatmark, T
影响因子：
5.6
作者：
Guerois, R;Nielsen, JE;Serrano, L
通讯作者：
Serrano, L
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
2.9
作者：
Forman, Julia R.;Worth, Catherine L.;Blundell, Tom L.
通讯作者：
Blundell, Tom L.
影响因子：
2.4
作者：
Counago, Rafael;Wilson, Corey J.;Shamoo, Yousif
通讯作者：
Shamoo, Yousif