Structural genomics is a field of genomics that involves the characterization of genome structures. This knowledge can be useful in the practice of manipulating the genes and DNA segments of a species.
As an example, it is important to understand the locus of a gene within the genome before it is possible to clone the gene successfully. Likewise, knowledge about the composition of the gene is useful when attempting to understand its function and how it can be altered for practical purposes, such as to ultimately improve health.
Structural genomics describes the 3-dimensional structure of each and every protein that may be encoded by a genome – when specifically analyzing proteins, this is more commonly referred to as structural proteomics. The study is aimed to study the structure of the entire genome, by utilizing both experimental and computational techniques. Whilst traditional structural prediction focuses on the structure of a particular protein in question, structural genomics considers a larger scale by aiming to determine the structure of every constituent protein encoded by a genome.
Objectives of structural genomics
It is hoped that more extensive knowledge of the structure of genomes, and comparing different examples, could lead to the deduction of principles that govern overall genomic structure.
As the protein structure and function are closely linked, the importance of structural genomics in understanding the function of proteins is paramount. Structural genomics can also provide insight in dynamic properties such as protein folding and identify possible targets that may be used for drug discovery.
Process and techniques
In the initial stages of structural genomics for a particular genome, genes and markers are assigned to individual chromosomes. As the chromosomal map becomes clearer, the depth of the analysis is increased to uncover more details about the structure. Eventually, the resolution of the analysis reaches a level sufficient to sequence the gene.
There are various techniques that may be used to determine the structure of the genome, which are often used in combination. These may include:
- De novo methods: every open reading frame (ORF) can be cloned and expressed as protein in complete genome sequences. The purified and crystallized proteins can be analyzed with X-ray crystallography or Nuclear Magnetic Resonance. This allows the structure of every protein encoded by the genome to be determined.
- Ab initio modeling: information about the protein sequence and amino acid interactions is used to predict the 3D structure of proteins.
- Sequenced-based modeling: compares the gene sequence of the protein with other protein sequences of a known structure. It uses protein homology to create a model for the structure of the unknown protein.
- Threading: uses similarities in the structural modeling and folding of the unknown protein with a protein of a known structure to model the structure of the new protein.
Sharing the structural findings
Structural genomics promotes the ability to share all new findings about protein structures with other members of the scientific community immediately.
However, many of the structures that are published are not associated with any known function. As a result, there are no corresponding research papers on the subject at hand to allow for building upon the work. Therefore, there is a need to communicate the new findings about genomic structures to other researchers so that the structural information can be utilized to investigate the function of the protein or subject being considered.
Reviewed by Afsaneh Khetrapal BSc (Hons)