Structural Bioinformatics by Unknown

Author:Unknown
Language: eng
Format: epub
Published: 2021-07-04T16:00:00+00:00

CONCLUSIONS

We have seen in this chapter that structure-function relationships are key to understand in molecular terms how a protein works. Structural data can complement experimental work; for example, if it is known from biochemical experiments that a particular protein of interest binds ATP, the structure of the protein complexed with an analogue of ATP will reveal exactly where ATP binds. It will also identify the residues on the protein that might stabilize the interaction between ligand and protein, and the potential structural consequences of ligand binding.

Structural data can also guide experimental work in eliciting the function of a protein. For example, if one can infer from structural homology that a particular protein is a hydrolase with a nucleotide binding domain, one can carry out experiments to confirm this and even identify possible substrates.

As structural genomics projects progress, determining protein function from structure with no prior knowledge of the function will become increasingly important. As described, a great number of methods exist to do this, and several servers have been developed to integrate the information from multiple sources in an attempt to improve predictions. However, there are still many proteins for which no functional information can be inferred from any existing method and therefore there is still a need to develop new methods to address these problematic structures. To date the methods that work best rely on the recognition of different homologues—identified either by whole fold matching or by local template matching.

When automatically assigning function to proteins, great care must be taken annotating those that are distantly related, so as to maintain accuracy in the databases. This is made more difficult by the fact that functions can differ in proteins that are almost identical and the converse is also true with examples of similar function in very different proteins. Ultimately, however, function will need to be assessed experimentally and this is a time-consuming process. In order to address this potential bottleneck, several high-throughput approaches to enzyme function assays and ligand binding assays have been developed to allow mass screening for specific functions.

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