This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
Chemical genetics
Chemical genetics uses small molecules that can interact with proteins to affect their function. This allows geneticists to determine how molecular function relates to structure. [1] Chemical genetics is also used for drug discovery by screening small molecules for for their potential to produce tools for biomedical research. [2] Small molecule discovery is usually performed by creating chemical libraries that are then tested with assays to look for protein binding partners. These results can then be used to draw conclusions about protein function or potential drug targets. [3]
When carrying out a chemical screen, the first decision is whether to use a diversity-oriented library or focused library. When little knowledge is known about potential chemical interaction partners, a diversity-oriented library that includes chemicals with a variety of different core structures (as shown in Figure 1A) is often chosen. In contrast, if a protein is known to interact with a given chemical, a focused library can be used that keeps the core chemical structure intact but makes other minor changes (as shown in Figure 1B) in order to determine new potential binding partners.
When carrying out a chemical screen, the first decision is whether to use a diversity-oriented library or focused library. When little knowledge is known about potential chemical interaction partners, a diversity-oriented library that includes chemicals with a variety of different core structures (as shown in Figure 1A) is often chosen. In contrast, if a protein is known to interact with a given chemical, a focused library can be used that keeps the core chemical structure intact but makes other minor changes (as shown in Figure 1B) in order to determine new potential binding partners.
Following the creation of a chemical library, potential interaction partners are then tested using high thoroughput assays that can detect small molecule-protein interactions. Two potential methods include either the small molecule (Figure 2A) or protein of interest (Figure 2B) being attached to a surface and its potential interaction partner can be added in solution to look for interactions. Once an interaction has been identified, the affect of this interaction on function of that protein can be studied. The results of past chemical genetic experiments can be searched in the PubChem and Chembank databases to find previously identified interaction partners that could be further explored or as a starting point for a focused chemical library.
Chemical genetics and tubby
After searching PubChem and and Chembank, I was unable to find any potential small molecule interactions with tubby or under the search term obesity. There were, however, a large number of molecules implicated in metabolic processes, one of tubby's GO biological function terms. These molecules could be used as a starting point for focused libraries in the future to determine if any are substrates of tubby. Similarly, a diversity-oriented library could also be created to look for a broader range of potential chemical interaction partners.
references
Cover Photo Credit
[1] HHMI. "Small Molecule Diversity." accessed 22 April 2014.
[2] Conrad Prebys Center for Chemical Genomics. "Reinventing how new drugs are discovered." accessed 22 April 2014.
[3] Stockwell, B.R. (2004). Exploring biology with small organic molecules. Nature. 432(7019), 846. doi: 10.1038/nature03196
[1] HHMI. "Small Molecule Diversity." accessed 22 April 2014.
[2] Conrad Prebys Center for Chemical Genomics. "Reinventing how new drugs are discovered." accessed 22 April 2014.
[3] Stockwell, B.R. (2004). Exploring biology with small organic molecules. Nature. 432(7019), 846. doi: 10.1038/nature03196
Site created by Rachael Baird.
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-10-14
Genetics 564 Assignment, Spring 2014
University of Wisconsin-Madison
Last Updated: 5-10-14