2005
DOI: 10.1128/jvi.79.19.12477-12486.2005
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Comprehensive Bioinformatic Analysis of the Specificity of Human Immunodeficiency Virus Type 1 Protease

Abstract: Rapidly developing viral resistance to licensed human immunodeficiency virus type 1 (HIV-1) protease inhibitors is an increasing problem in the treatment of HIV-infected individuals and AIDS patients. A rational design of more effective protease inhibitors and discovery of potential biological substrates for the HIV-1 protease require accurate models for protease cleavage specificity. In this study, several popular bioinformatic machine learning methods, including support vector machines and artificial neural … Show more

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Cited by 55 publications
(27 citation statements)
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“…About 746 peptides with 8 residues were widely culled by You et al [19] , and several models for prediction of cleavage sites were developed. Although the representation of the sequences was carried out using three different methods, i.e., the similarity matrix distance method, the sparse orthogonal coding scheme method, and the property coding method, the methodology of representation of sequences of peptides was not the focus of the present work.…”
Section: Data Setmentioning
confidence: 99%
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“…About 746 peptides with 8 residues were widely culled by You et al [19] , and several models for prediction of cleavage sites were developed. Although the representation of the sequences was carried out using three different methods, i.e., the similarity matrix distance method, the sparse orthogonal coding scheme method, and the property coding method, the methodology of representation of sequences of peptides was not the focus of the present work.…”
Section: Data Setmentioning
confidence: 99%
“…Hence, a better understanding of the HIV PR specificity, i.e., knowing which amino acid sequences are cleaved by the protease and which are not, is necessary for developing more efficient inhibitors. This is, however, difficult since it cleaves at several different sites that have little or no sequence similarity [4] . The HIV PR has an active site with eight subsites, and it can be named S4-S3-S2-S1-S1'-S2'-S3'-S4' [5] .…”
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confidence: 99%
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“…746: 746 exemplars (401 cleaved, 345 noncleaved) 14 1625: 1,625 exemplars (374 cleaved, 1251 noncleaved) 8 Schilling: 3,272 exemplars (434 cleaved, 2,838 noncleaved) 15 Impens: 947 exemplars (149 cleaved, 798 noncleaved)collected from 4 publications [16][17][18][19] This corresponds to a total of 6,590 exemplars, of which 1,358 represent HIV-1 protease cleavages. These 4 data sets contain 740 repeated exemplars, and 10 octamers with different classifications in different sets.…”
Section: Introductionmentioning
confidence: 99%
“…We test the generality of that proposal by using these transfer free energies as a 2D basis set to predict cleavage rates for 140 variants of the cleavage sites processed by the HIV-1 protease, based on 6 natural cleavage sites processed during virus maturation. Previous work [3,4] attributed mutational perturbations of HIV-1 protease cleavage rates qualitatively to the size and polarity of the eight residues in the protease recognition site. Wild type sequences for six of the nine cleavage sites are cleaved at rates that vary over a range of nearly three orders of magnitude.…”
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confidence: 99%