Protein function predictions

Skolnick J, BryKnski M (2009) FINDSITE a combined evolution/structure-based approach to protein function prediction. Brief Bioinform 10 378-391... 

Gabaldon T (2005) Origin and evolution of the mitochondrial proteome. Applications for protein function prediction in the eukaryotes. Thesis, Nijmegen Gabaldon T, Huynen MA (2003) Reconstruction of the proto-mitochondrial metabolism. Science 301 609-609... 

Similar research has attempted to gain insight into protein function prediction based on information hidden in the molecular structure of metabolites (35). Such work may eventually identify the relationship between metabolite structure and protein function, thus possibly improving techniques in the prediction of enzyme function and novel metabolic pathways (36). 

Nemati, S., Basiri, M.E., Ghasem-Aghaee, N., Aghdam, M.H. A novel ACO-GA hybrid algorithm for feature selection in protein function prediction. J. Expert Syst. Appl. Int. J. Arch. 36(10), 12086-12094 (2009)... 

Chua, H. N., W. K. Simg, and L. Wong. (2007). An efficient strategy for extensive integration of diverse biological data for protein function prediction. Bioinformatics 23 3364-3373 Dec 15. 

Moult J, T Hubbard, K Fldelis and J T Pedersen 1999. Critical Assessment of Methods of Protein Structure Prediction (CASP) Round III. Proteins Structure, Function and Genetics Suppl. 3 2-6. 

L Rychlewski, B Zhang, A Godzik. Fold and function predictions for Mycoplasma genitalmm proteins. Fold Des 3 229-238, 1998. 

Raha K, Merz KM. Large-scale validation of a quantum mechanics based scoring function predicting the binding affinity and the binding mode of a diverse set of protein-ligand complexes. J Med Chem 2005 48 4558-75. 

If two genes (white and black circles) are found as neighbors in several genomes, the encoded proteins are predicted to functionally interact. Figure adapted from Eisenberg etal. (2000). 

Fig. 12.5. Schematic summary of the eight T. canis proteins containing predicted SXC (NC6) domains. The consensus is shown in the N-terminal domain of PEB-1 (phosphatidylethanolamine-binding protein-1) as xCxDxxxDC(6x)C(11x) RCxxTCxxC. This consensus is faithfully repeated in MUC-1 (mucin-1), MUC-2, MUC-4 and MUC-5, and in all but the C-terminal domain of MUC-3. This domain (and the C-terminal SXC domain of PEB-1) show consensus spacing but some variation in consensus residues. Two additional proteins with quadrupled SXC domains differ in spacing between cysteines-2, -3 and -4, and show more variation in consensus residues. These are VAH-1 (venom allergen homologue) and HUF-001 (homologue of unknown function-001).

The ultimate goal of structural genomics is to provide a complete three-dimensional description of any gene product. Also, as the structures of more and more proteins of known function are elucidated, it should become increasingly possible to link specific functional attributes to specific structural attributes. As such, it may prove ultimately feasible to predict protein function if its structure is known, and vice versa. 

KING, R.D., KARWATH, A., CLARE, A., DEHASPE, L., Accurate prediction of protein functional class from sequence in Mycobacterium tuberculosis and Escherichia coli genomes using data mining, Yeast, 2000,17, 283-293. 

Smith, 1992). All of these can identify an optimal alignment between the query and either a set of previously studied sequences or a pattern of sequence elements identified as common to a set of previously studied proteins. De novo sequence analysis methods have proved less useful. Although there has been some slow progress in predicting a protein s structure from its sequence, no direct functional predictions methods have been developed. 

A major problem in function prediction is the multidomain nature of many proteins, where a protein can be assigned die function of another, even though it may only share a single common domain. Such... 

Koonin, E. V., Mushegian, A. R., Galperin, M. Y., and Walker, D. R. (1997). Comparison of archaeal and bacterial genomes computer analysis of protein sequences predicts novel functions and suggests a chimeric origin for the archaea. Mol. Microbiol. 25, 619-637. 

Pawlowski, K, Zhang, B., Rychlewski, L., and Godzik, A. (1999). The Helicobacter pylori genome from sequence analysis to structural and functional predictions. Proteins 36, 20-30. 

The identification of the fold is, however, only a minor part of protein characterization. Function is a loosely defined term, but must be viewed within a particular context, e.g., protein function can only take place with an interaction partner or within cellular cascades and networks. Fold predictions and homology searches can only give partial answers to such higher order functions. Thus, independent functional features have to be collected and put into context. Such features include not only molecular properties, but also cellular roles, expression patterns, dysfunctions, pathway context, and subcellular localization. The latter can be predicted by exploiting a variety of methods and localization sites. Kenta Nakai reviews many such sites and their implementation... 

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