Fariselli P, Casadio R
CIRB Biocomputing Unit, Laboratory of Biophysics, Department of Biology, University of Bologna, via Irnerio 42, 40126 Bologna, Italy.
Bioinformatics. 2001 Oct;17(10):957-64. doi: 10.1093/bioinformatics/17.10.957.
A major problem in protein structure prediction is the correct location of disulfide bridges in cysteine-rich proteins. In protein-folding prediction, the location of disulfide bridges can strongly reduce the search in the conformational space. Therefore the correct prediction of the disulfide connectivity starting from the protein residue sequence may also help in predicting its 3D structure.
In this paper we equate the problem of predicting the disulfide connectivity in proteins to a problem of finding the graph matching with the maximum weight. The graph vertices are the residues of cysteine-forming disulfide bridges, and the weight edges are contact potentials. In order to solve this problem we develop and test different residue contact potentials. The best performing one, based on the Edmonds-Gabow algorithm and Monte-Carlo simulated annealing reaches an accuracy significantly higher than that obtained with a general mean force contact potential. Significantly, in the case of proteins with four disulfide bonds in the structure, the accuracy is 17 times higher than that of a random predictor. The method presented here can be used to locate putative disulfide bridges in protein-folding.
The program is available upon request from the authors.
蛋白质结构预测中的一个主要问题是富含半胱氨酸的蛋白质中二硫键的正确定位。在蛋白质折叠预测中，二硫键的位置可以极大地减少构象空间中的搜索。因此，从蛋白质残基序列开始正确预测二硫键连接性也可能有助于预测其三维结构。
在本文中，我们将预测蛋白质中二硫键连接性的问题等同于寻找最大权重图匹配的问题。图的顶点是形成二硫键的半胱氨酸残基，权重边是接触势。为了解决这个问题，我们开发并测试了不同的残基接触势。基于埃德蒙兹 - 加博算法和蒙特卡罗模拟退火的表现最佳的接触势，其准确率显著高于使用一般平均力接触势所获得的准确率。值得注意的是，对于结构中有四个二硫键的蛋白质，其准确率比随机预测器高17倍。这里提出的方法可用于在蛋白质折叠中定位假定的二硫键。
该程序可根据作者要求提供。
