From Protein Structure to Function with Bioinformatics.pdf

314 I.A. Cymerman et al.12.5 What Next?Despite the usefulness of protein modelling, not all biologists take full advantageof the insights into protein function that it offers. Easy access to the reliablemodels provided by the different models repositories is the first step towardsestablishing a dialogue between modellers and experimental biologists. Thisinteraction between the two communities is not only mutually beneficial butalso necessary for the effective development of both disciplines. Structuralmodels can greatly facilitate the planning and interpretation of bench experiments,as they restrict the number of hypotheses to test and sometimes providevery precise suggestions about experiments to perform. Thus, we propose thatthe recently advocated efforts to identify the so far unknown proteins thatencode known enzymatic activities (Roberts 2004) should be integrated withmodelling efforts that can bridge the gap between the set of functions for whichproteins are sought, and sets of uncharacterized sequences for which functionsshould be predicted.On the other hand it must be remembered that the current catalogue of functionsis restricted to empirically determined activities. In other words, function predictionis typically carried out by seeking for a match to a function that is already known,and less commonly by inferring a function that may be possible but has not yet beenobserved. In other words, there are basically no methods to predict functionde novo. Thus, while the development of such new computational approachesshould be encouraged, the existing knowledge-driven methods require the experimentalmethods to identify new reactions and processes that could be then mappedonto the database of protein sequences and structures. The experimental analysesbecome even more important in the light of recent data showing that the rate ofnovel protein families discovery is approximately linear (Yooseph et al. 2007) andthat we are far from being able to draw reliable conclusions about the dimensionsof protein function space on earth (Raes et al. 2007).ReferencesAloy P, Russell RB (2002) Interrogating protein interaction networks through structural biology.Proc Natl Acad Sci USA 99:5896–5901Aloy P, Russell RB (2003) InterPreTS: protein interaction prediction through tertiary structure.Bioinformatics 19:161–162Aloy P, Russell RB (2006) Structural systems biology: modelling protein interactions. Nat RevMol Cell Biol 7:188–197Baxter SM, Rosenblum JS, Knutson S, et al. (2004) Synergistic computational and experimentalproteomics approaches for more accurate detection of active serine hydrolases in yeast. MolCell Proteomics 3:209–225Bonneau R, Strauss CE, Rohl CA, et al. (2002) De novo prediction of three-dimensional structuresfor major protein families. J Mol Biol 322:65–78Bradley P, Misura KM, Baker D (2005) Toward high-resolution de novo structure prediction forsmall proteins. Science 309:1868–1871