A new ensemble coevolution system for detecting HIV-1 protein coevolution
"Background: A key challenge in the field of HIV-1 protein evolution is the identification of coevolving amino acids at the molecular level. In the past decades, many sequence-based methods have been designed to detect position-specific coevolution within and between different proteins. However, an ensemble coevolution system that integrates different methods to improve the detection of HIV-1 protein coevolution has not been developed. Results: We integrated 27 sequence-based prediction methods published between 2004 and 2013 into an ensemble coevolution system. This system allowed combinations of different sequence-based methods for coevolution predictions. Using HIV-1 protein structures and experimental data, we evaluated the performance of individual and combined sequence-based methods in the prediction of HIV-1 intra- and inter-protein coevolution. We showed that sequence-based methods clustered according to their methodology, and a combination of four methods outperformed any of the 27 individual methods. This four-method combination estimated that HIV-1 intra-protein coevolving positions were mainly located in functional domains and physically contacted with each other in the protein tertiary structures. In the analysis of HIV-1 inter-protein coevolving positions between Gag and protease, protease drug resistance positions near the active site mostly coevolved with Gag cleavage positions (V128, S373-T375, A431, F448-P453) and Gag C-terminal positions (S489-Q500) under selective pressure of protease inhibitors. Conclusions: This study presents a new ensemble coevolution system which detects position-specific coevolution using combinations of 27 different sequence-based methods. Our findings highlight key coevolving residues within HIV-1 structural proteins and between Gag and protease, shedding light on HIV-1 intra- and inter-protein coevolution. Reviewers: This article was reviewed by Dr. Zoltán Gáspári. © Li et al."
Human immunodeficiency virus 1 ; gag ; Human Immunodeficiency Virus ; Molecular ; Molecular ; Protein ; Statistical ; Tertiary ; Gag protein ; Human immunodeficiency virus proteinase ; Protein binding ; Viral protein ; Area under the curve ; Biology ; Chemistry ; Genetics ; Human ; Human immunodeficiency virus 1 ; Molecular evolution ; Molecular model ; Procedures ; Protein database ; Protein tertiary structure ; Reproducibility ; Statistical model ; Area Under Curve ; Computational Biology ; Databases ; Evolution ; Gag Gene Products ; Gene Products ; HIV Protease ; HIV-1 ; Humans ; Models ; Models ; Protein Binding ; Protein Structure ; Reproducibility of Results ; Viral Proteins ; Ensemble coevolution system ; Gag ; HIV-1 ; Protease ; Protein coevolution ; Sequence-based method ;
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