Abstract
HIV-1 protease has a broad and complex substrate specificity. The discovery of an accurate, robust, and rapid method for predicting the cleavage sites in proteins by HIV protease would greatly expedite the search for inhibitors of HIV protease. During the last two decades, various methods have been developed to explore the specificity of HIV protease cleavage activity. However, because little advancement has been made in the understanding of HIV-1 protease cleavage site specificity, not much progress has been reported in either extracting effective methods or maintaining high prediction accuracy. In this article, a theoretical framework is developed, based on the kernel method for dimensionality reduction and prediction for HIV-1 protease cleavage site specificity. A nonlinear dimensionality reduction kernel method, based on manifold learning, is proposed to reduce the high dimensions of protease specificity. A support vector machine is applied to predict the protease cleavage. Superior performance in comparison to that previously published in literature is obtained using numerical simulations showing that the basic specificities of the HIV-1 protease are maintained in reduction feature space, and by combining the nonlinear dimensionality reduction algorithm with a support vector machine classifier.
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Acknowledgments
This study is supported by Foundation of National Natural science No.10671030. We are very grateful to Prof. J.F. Wang for guidance on information acquisition and technical assistance on proteases.
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Li, X., Hu, H. & Shu, L. Predicting human immunodeficiency virus protease cleavage sites in nonlinear projection space. Mol Cell Biochem 339, 127–133 (2010). https://doi.org/10.1007/s11010-009-0376-y
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DOI: https://doi.org/10.1007/s11010-009-0376-y