Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (03): 318-324.DOI: 10.6023/A1106042 Previous Articles     Next Articles

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基于VHSE 结构表征的蛋白酶体酶切位点预测及酶切特异性研究

谢江安a, 梅虎a,b, 吕娟a, 潘显超a, 王青a, 张亚兰a   

  1. a 生物流变科学与技术教育部重点实验室 重庆大学 重庆 400044;
    b 重庆大学生物工程学院 重庆 400044
  • 投稿日期:2011-06-04 修回日期:2011-09-04 发布日期:2011-10-26
  • 通讯作者: 梅虎
  • 基金资助:

    重庆市自然科学基金重点项目(CSTC, 2009BA5068)和重庆大学中央高校基本科研业务费科研专项(CDJXS, 11231177)资助项目.

Studies on the Prediction of Selective Cleavage Sites and Cleavage Profile of Proteasome Using VHSE Amino Acid Descriptor

Xie Jiangana, Mei Hua,b, Lü Juanba, Pan Xianchaoa, Wang Qinga, Zhang Yalana   

  1. a Key Laboratory of Biorheological Science and Technology Ministry of Education, Chongqing University, Chongqing 400044;
    b College of Bioengineering, Chongqing University, Chongqing 400044
  • Received:2011-06-04 Revised:2011-09-04 Published:2011-10-26
  • Supported by:

    Project supported by Chongqing Key Natural Science Foundation (No. 2009BA5068), and the Fundamental Research Funds for the Central Universities (No. 11231177).

The ubiquitin-proteasome system (UPS) plays a critical role in proteolysis and degradation in many physiological processes of the eukaryotes, such as antigen presentation, cell cycle regulation, and transcription factors activation. Recently, due to the importance of selective substrate cleavage of proteasome in the UPS, the cleavage site prediction has attracted considerable interest in computational biology. However, the existing methods are mostly based on nonlinear models with little physicochemical meanings. In this paper, VHSE (Principal component score vector of hydrophobic, steric, and electronic properties), a novel set of amino acid descriptors, was used to characterize the source proteins of 2650 natural MHC class I ligands. Based on the structural descriptions of the amino acids adjacent to the cleavage site, support vector machine (SVM) was then employed to establish the prediction models using linear and RBF kernel functions. A linear SVM model with high prediction capability was obtained, of which the sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and the Matthews correlation coefficient (MCC) were 0.9018, 0.6963, 0.8797 and 0.6131, respectively. The results showed that the hydrophobic, electronic, and steric properties of the amino acids adjacent to the cleavage site are closely related to the selective substrate cleavage, especially for those at the positions of P9, P8, P4, P1, P3', P4', and P5'. The results also showed that hydrophobic potential difference between P1 position and P1'~P5' positions may benefit the cleavage process of the proteasome.

Key words: proteasome, MHC-I ligand, VHSE, SVM, cleavage site