Structural genomics

Structural genomics consists in the determination of the three dimensional structure of all proteins of a given organism, by experimental methods such as X-ray crystallography, NMR spectroscopy or computational approaches such as homology modelling.

As opposed to traditional structural biology, the determination of a protein structure through a structural genomics effort often (but not always) comes before anything is known regarding the protein function. This raises new challenges in structural bioinformatics, i.e. determining protein function from its 3D structure.

Structural genomics emphasizes high throughput determination of protein structures. This is performed in dedicated centers of structural genomics.

While most structural biologists pursue structures of individual proteins or protein groups, specialists in structural genomics pursue structures of proteins on a genome wide scale. This implies large scale cloning, expression and purification. One main advantage of this approach is economy of scale. On the other hand, the scientific value of some resultant structures is at times questioned. A Science article from January 2006 analyzes the structural genomics field.

One advantage of structural genomics, such as the Protein Structure Initiative, is that the scientific community gets immediate access to new structures, as well as to reagents such as clones and protein. A disadvantage is that many of these structures are of proteins of unknown function and do not have corresponding publications. This lack of publications is not entirely unanticipated in that a change in the way how protein structures are determined would require corresponding changes in the way this structural information is communicated to the broader research community. The Bioinformatics core of the Joint center for structural genomics (JCSG) has recently developed a wiki-based approach namely The Open Protein Structure Annotation Network (TOPSAN) for annotating protein structures emerging from high-throughput structural genomics centers. Some of the pros and cons of the Protein Structure Initiative are discussed in the December 2007 and January 2008 issues of the journal Structure. It is sometimes assumed that the technical quality of structural genomics structures is lower than that of traditional structures, but this has been shown to be false.