Interacting protein databases

Recently, an interactive protein database that integrates the spots with the 2-DE map for HCC-M has been created. It is now freely accessible on the World Wide Web at http //proteome.btc.nus.edu.sg/hccm/ (Eiang et ah,... 

Figure 5.11. Generic approaches to identify interacting proteins within complexes. The complex is isolated from cells by affinity purification using a tag sequence attached to a protein known to be in the complex. Alternatively, the complex can be immunprecipitated with an antibody to one of the proteins in the complex. The proteins are resolved by polyacrylamide gel electrophoresis, proteolyzed, and the mass of the resulting peptides is determined by mass spectrometry. Alternatively, the proteins can be proteolyzed and the resulting peptides resolved by liquid chromatography. The peptide masses are then determined by mass spectrometry and used for database searching to identify the component proteins.

The experimental exploration and confirmation of protein functions are relatively slow processes and always require dedicated experiments. The analysis of protein-protein associations as such improved remarkably in quality and speed. This is accompanied by the creation of new databases that will reflect the network of interacting proteins (the Protein Function and Metabolic Pathway project, http //bioinformer.ebi. ac.uk 80/newsletter/archives/4/pfmp.html, and the Biomolecular Interaction Network Database project http //bioinfo.mshri.on.ca/ BIND/). These activities contribute to the idea that cellular mechanisms can be better understood when they are seen as a multicomponent networked process. 

PSI-BLAST (Altschul et al., 1997) is rapidly becoming the tool of choice for protein database searching because of its speed, sensitivity and ease of use. It presents a very large improvement over the older versions of BLAST and new gapped-BLAST implementations (Altschul et al., 1997 Altschul et al., 1990). However, a naive user can easily be misled or not get the best possible results. PSI-BLAST is available as a stand-alone program from ftp //and as an interactive web tool at http //www.ncbi. nlm.nih.gov/cgibin/BLAST/nph-psi blast... 

The Database of Interacting Proteins (DIP) stores information about experimentally determined interactions between proteins see Table 1.3). Users can search the... 

Protein-drug Interaction Drug ADME (Absorption, Distribution, Metabolism, and Excretion) Associated Protein Database http //xin.cz3.nus.edu.sg/group/admeap/ admeap.asp Drug ADME-associated proteins... 

To Study interactions between proteins and drugs, an available tool is the Drug Absorption, Distribution, Metabolism, and Excretion (ADME) Associated Protein Database (see Table 1.5). The database contains information about relevant proteins, functions, similarities, substrates and hgands, tissue distributions, and other features of targets. Eor the understanding of pharmacokinetic (PK) and pharmacodynamic (PD) features, some available resources are listed in Table 1.5. For example, the Pharmacokinetic and Pharmacodynamic Resources site provides links to relevant software, courses, textbooks, and journals (see Note 5). For quantitative structure-activity relationship (QSAR), the QSAR Datasets site collects data sets that are available in a structural format (see Table 1.5). 

The requirement that all elements match may seem a harsh criterion, but even if this is relaxed, the conclusions of the resulting model are not radically different. It should also be noted that, in the published protein database structures, only one structure of a protein-ligand complex exists where a wrong interaction is observed and cannot be rationalized by, for example, the mediation of an unobserved water molecule [15]. 

Lysozyme and Antibodies To fully appreciate how proteins function in a cell, it is helpful to have a three-dimensional view of how proteins interact with other cellular components. Fortunately, this is possible using on-line protein databases and the three-dimensional molecular viewing utilities Chime and Protein Explorer. If you have not yet installed the Chime plug-in on your computer, go to www.mdlchime.com/chime and follow the instructions for your operating system and browser. Once chime is installed, go to the Protein Data Bank (www.rcsb.org/pdb). 

Small peptide phage libraries have been used to screen for binding to organic molecules to identify consensus motifs that are then compared to known protein sequences to eventually determine biologically relevant interactions. Rodi et al. (80) screened a commercially available 12-mer library L6 fused to phage pill coat protein for its binding with a biotinylated derivative of taxol supported onto streptavidin-coated petri dishes (Fig. 10.15). The isolated sequences after one, two, and three rounds of selection and amplification were compared for common structural motifs. Two 5-mer motifs were identified, and a search in protein databases found six binding candidates for taxol (Fig. 10.15). More sophisticated... 

Database of interacting proteins http //dip.doe-mbi.ucla.edu also dictionary of interfaces in proteins http //drug-redesign.de/superposition.html 3-[A,/V-bis(2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid Dynamic light scattering... 

The database of interacting proteins integrates the experimental evidence available on protein interactions into a single on-line resource http //dip. doe-mbi.ucla.edu. See Xenarious, L, Fernandez, E., Salwinski, L., Duan, X.J. et al., DIP the database of interacting proteins 2001 update. Nucleic Acids Res. 29, 239-241, 2001 Deane, C.M., Salwinski, L., Xenarios, L,... 

Salwinskr, L., Miller, C.S., Smith, A.J., Pettit, F.K., Bowie, J.U. and Eisenbetg, D. (2004) The Database of interacting proteins 2004 update. Nucleic Acids Res. 32, D449-D451. 

Xenarios, I., L. Salwinski, X. J. Duan, R Higney, S. M. Kim, and D. Eisenberg. 2002. DIP, the Database of Interacting Proteins A research tool for studying cellular networks of protein interactions. Nucleic Acids Res 30 303-5. 

The Database of Interacting Proteins (DIP) [Salwinski et al. 2004] encompasses protein-protein interaction data. DIP started life as an academic project, but since 2001 has been generally available under commercial license. 

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