Instruction: What is structural genomics?

Response: Structural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome. This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling approaches. The principal difference between structural genomics and traditional structural prediction is that structural genomics attempts to determine the structure of every protein encoded by the genome, rather than focusing on one particular protein. With full-genome sequences available, structure prediction can be done more quickly through a combination of experimental and modeling approaches, especially because the availability of large number of sequenced genomes and previously solved protein structures allows scientists to model protein structure on the structures of previously solved homologs.

Because protein structure is closely linked with protein function, the structural genomics has the potential to inform knowledge of protein function. In addition to elucidating protein functions, structural genomics can be used to identify novel protein folds and potential targets for drug discovery. Structural genomics involves taking a large number of approaches to structure determination, including experimental methods using genomic sequences or modeling-based approaches based on sequence or structural homology to a protein of known structure or based on chemical and physical principles for a protein with no homology to any known structure.

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 requires new ways of communicating this structural information to the broader research community. The Bioinformatics core of the Joint center for structural genomics (JCSG) has recently developed a wiki-based approach namely Open protein structure annotation network (TOPSAN) for annotating protein structures emerging from high-throughput structural genomics centers.