Most protein-ligand interactions take place on surfaces and include but not limited to factors such as chemical composition, hydrophobicity, electronegavitiy and shape complementarity. Past studies showed that protein...Most protein-ligand interactions take place on surfaces and include but not limited to factors such as chemical composition, hydrophobicity, electronegavitiy and shape complementarity. Past studies showed that protein-protein interactions occur on comparatively fiat regions whereas protein-ligand bindings involve crevices. In the search for such sites various approaches have been designed and developed each of which is algorithmically unique. The use of grid units or voxels has been demonstrated in early studies with relatively good results obtained. We present here an approximated approach comprising of the use of voxels and computer vision methods in the search for ligand-binding areas. Each test protein is modelled and analysed in 2D with all corresponding residues graphically presented for successfully identified sites. The study was carried out on 2 sets of proteins： FK506-bound proteins and heme-bound proteins with promising results obtained for all test cases.展开更多
Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the...Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the signaling molecules of some signaling pathways have been determined. In this paper, we propose a novel hybrid intelligent method, namely HISP （Hybrid Intelligent approach for identifying directed Signaling Pathways）, to determine both the topologies of signaling pathways and the direction of signaling flows within a pathway based on integer linear programming and genetic algorithm. By integrating the protein-protein interaction, gene expression, and gene knockout data, our HISP approach is able to determine the optimal topologies of signaling pathways in an accurate way. Benchmark results on yeast MAPK signaling pathways demonstrate the efficiency of our proposed approach. When applied to the EGFR/ErbB signaling pathway in human hepatocytes, HISP unveils a high-resolution signaling path- way, where many signaling interactions were missing by existing computational approaches.展开更多
文摘Most protein-ligand interactions take place on surfaces and include but not limited to factors such as chemical composition, hydrophobicity, electronegavitiy and shape complementarity. Past studies showed that protein-protein interactions occur on comparatively fiat regions whereas protein-ligand bindings involve crevices. In the search for such sites various approaches have been designed and developed each of which is algorithmically unique. The use of grid units or voxels has been demonstrated in early studies with relatively good results obtained. We present here an approximated approach comprising of the use of voxels and computer vision methods in the search for ligand-binding areas. Each test protein is modelled and analysed in 2D with all corresponding residues graphically presented for successfully identified sites. The study was carried out on 2 sets of proteins： FK506-bound proteins and heme-bound proteins with promising results obtained for all test cases.
文摘Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the signaling molecules of some signaling pathways have been determined. In this paper, we propose a novel hybrid intelligent method, namely HISP （Hybrid Intelligent approach for identifying directed Signaling Pathways）, to determine both the topologies of signaling pathways and the direction of signaling flows within a pathway based on integer linear programming and genetic algorithm. By integrating the protein-protein interaction, gene expression, and gene knockout data, our HISP approach is able to determine the optimal topologies of signaling pathways in an accurate way. Benchmark results on yeast MAPK signaling pathways demonstrate the efficiency of our proposed approach. When applied to the EGFR/ErbB signaling pathway in human hepatocytes, HISP unveils a high-resolution signaling path- way, where many signaling interactions were missing by existing computational approaches.
