Screenshot of the taxonomic tree showing the distribution of the PHP domain (PF02811)

<p><b>Copyright information:</b></p><p>Taken from "GOTax: investigating biological processes and biochemical activities along the taxonomic tree"</p><p>http://genomebiology.com/2007/8/3/R33</p><p>Genome Biology 2007;8(3):R33-R33.</p><p>Published online 8 Mar 2007</p><p>PMCID:PMC1868936.</p><p></p> The corresponding query is: TAX WHERE PFAM:PF02811

Screenshot of the histogram showing the grouping of the biological processes from yeast with a semantic similarity below 0

<p><b>Copyright information:</b></p><p>Taken from "GOTax: investigating biological processes and biochemical activities along the taxonomic tree"</p><p>http://genomebiology.com/2007/8/3/R33</p><p>Genome Biology 2007;8(3):R33-R33.</p><p>Published online 8 Mar 2007</p><p>PMCID:PMC1868936.</p><p></p>6 to any process from human. The groups correspond to 'cellular physiological process' (GO:0050875), 'localization' (GO:0051179), 'metabolism' (GO:0008152), and 'regulation of physiological process' (GO:0050791)

Screenshot of the map of the functional space of Pfam families showing the comparison of families between human and yeast

<p><b>Copyright information:</b></p><p>Taken from "GOTax: investigating biological processes and biochemical activities along the taxonomic tree"</p><p>http://genomebiology.com/2007/8/3/R33</p><p>Genome Biology 2007;8(3):R33-R33.</p><p>Published online 8 Mar 2007</p><p>PMCID:PMC1868936.</p><p></p> The map of the functional space was obtained by multidimensional scaling [2]. Pfam families shared between human and yeast are colored pink. Green dots indicate Pfam families unique to yeast and yellow dots represent families unique to human. Pfam families colored black do not occur in either human or yeast. The colored contour lines represent the regions of different functions. For more information on the map see [2]. The following query was used: PFAM WHERE TAX:4932 PFAMCP PFAM WHERE TAX:9606

Mining GO Annotations for Improving Annotation Consistency

<div><p>Despite the structure and objectivity provided by the Gene Ontology (GO), the annotation of proteins is a complex task that is subject to errors and inconsistencies. Electronically inferred annotations in particular are widely considered unreliable. However, given that manual curation of all GO annotations is unfeasible, it is imperative to improve the quality of electronically inferred annotations. In this work, we analyze the full GO molecular function annotation of UniProtKB proteins, and discuss some of the issues that affect their quality, focusing particularly on the lack of annotation consistency. Based on our analysis, we estimate that 64% of the UniProtKB proteins are incompletely annotated, and that inconsistent annotations affect 83% of the protein functions and at least 23% of the proteins. Additionally, we present and evaluate a data mining algorithm, based on the association rule learning methodology, for identifying implicit relationships between molecular function terms. The goal of this algorithm is to assist GO curators in updating GO and correcting and preventing inconsistent annotations. Our algorithm predicted 501 relationships with an estimated precision of 94%, whereas the basic association rule learning methodology predicted 12,352 relationships with a precision below 9%.</p> </div

Manual evaluation of the 20 most supported rules selected by our GO relationship learning algorithm.

<p>Each association is classified as: true if evidence for a relationship between the terms was found; reverse if the reverse rule is true; unknown if no conclusive evidence was found for or against the association; and false if a counterexample was found. The support is given in number of co-annotations.</p

Rotameric states and conformational differences for V36 mutants A/G/L/M computed with IRECS using the PDB entry

The figure illustrates the relative position of mutant side chains (light grey) and the wild-type residue V36 (blue). The important carbon atoms of the side chains are indicated as C, Cand C. Protein backbone changes are depicted in black. The contribution of F43 to the hydrophobic cavity conformation and the cyclopropyl binding pocket is illustrated by means of a transparent surface patch.<p><b>Copyright information:</b></p><p>Taken from "Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus"</p><p>http://genomebiology.com/2008/9/1/R16</p><p>Genome Biology 2008;9(1):R16-R16.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2395260.</p><p></p

Network of non-covalent residue interactions for the NS3-4A protease and the corresponding list of protein-ligand interactions

Network analysis of non-covalent residue interactions for the NS3-4A protease (PDB entry ). Nodes represent residues and colored edges represent different types of interactions: van der Waals interactions, backbone-side chain (blue), side chain-side chain (red); H-bond interactions, backbone-side chain (green), side chain-side chain (orange). Protein-ligand interactions for the and ligands CPX and SCH 446211, respectively, as well as for VX-950 are tagged by brown Arabic numerals above each residue node (see (b)). Catalytic residues are yellow and the mutated residues are blue (V36), red (T54) and grey (R155, A156). List of van der Waals interactions (vdW), H-bonds (HB) and covalent bonds (CB) for the and ligands CPX and SCH 446211, respectively, and the VX-950 ligand docking result. Each dot or square represents one interaction of the ligand with an amino acid of the NS3-4A protease, and dots indicate interactions with the cyclopropyl group. Brown Arabic numerals refer to protein-ligand interactions in the network of non-covalent interactions (a).<p><b>Copyright information:</b></p><p>Taken from "Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus"</p><p>http://genomebiology.com/2008/9/1/R16</p><p>Genome Biology 2008;9(1):R16-R16.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2395260.</p><p></p

Visualization of the NS3-4A protease binding pocket (left) and the corresponding network of non-covalent residue interactions in the neighborhood of F43 (right)

For details, see the legend of Figure 5.<p><b>Copyright information:</b></p><p>Taken from "Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus"</p><p>http://genomebiology.com/2008/9/1/R16</p><p>Genome Biology 2008;9(1):R16-R16.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2395260.</p><p></p

NS3-4A protease domain of PDB structure with co-crystallized ligand CPX (yellow) 32 and a second ligand, SCH 446211 (light blue), taken from the superimposed PDB structure 30

The protease binding pocket from structure is shown as a transparent surface patch. The residues V36 and T54 are depicted as stick-and-ball models, located in the parallel β-strands β1 and β3 of an anti-parallel β-sheet (dark blue).<p><b>Copyright information:</b></p><p>Taken from "Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus"</p><p>http://genomebiology.com/2008/9/1/R16</p><p>Genome Biology 2008;9(1):R16-R16.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2395260.</p><p></p

Structure and network analysis of non-covalent residue interactions for T54

Left column: visualization of the NS3-4A protease structure and surface of the binding pocket of with co-crystallized ligands taken from two superimposed PDB structures: with ligand CPX (yellow) and with ligand SCH 446211 (light blue). Right column: corresponding network analysis of non-covalent residue interactions for T54 mutants. Residues presumed to interact with the cyclopropyl group of VX-950 are indicated by black dots. Nodes represent residues and colored edges represent different types of interactions (see Figure 4): van der Waals interactions, backbone-side chain (blue), side chain-side chain (red); H-bond interactions, backbone-side chain (green), side chain-side chain (orange). Anti-parallel β-sheet and H-bond interactions of T54 with L44 and V55 (yellow). H-bonds are shown as cyan dotted lines and corresponding distances printed in cyan. Loop-forming residues (orange) and hydrophobic pocket conformation. Impact of T54 mutants on the catalytic triad via the node V55 (purple).<p><b>Copyright information:</b></p><p>Taken from "Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus"</p><p>http://genomebiology.com/2008/9/1/R16</p><p>Genome Biology 2008;9(1):R16-R16.</p><p>Published online 23 Jan 2008</p><p>PMCID:PMC2395260.</p><p></p