The Center for Structural Biology uses structure based drug design, high throughput screening, an extensive compound library, and many other facilities in order to promote the advancement of research in drug discovery, biochemistry, microbiology and multiple other fields.
Structure Based Drug Design
Structure Based Drug Design (SBDD) is a process of developing drugs against a target based on the structure of the target. Traditional high through-put methods of drug development are based on luck - screening a library of random compounds in the hopes of finding a compound that acts against the target. This method is expensive and has a very low success rate. However, it is possible to tailor a potential drug to a target by using the wealth of structural information currently available, this is the basis for SBDD.
Many drugs are enzyme inhibitors which bind the protein's active site and inhibit the natural reaction from occurring.
By recognizing the interactions in the active site with the natural substrate or any known inhibitors, it is possible to design a new compound which can inhibit the activity of the enzyme. As more structural information becomes available, our understanding of the chemical interplay within molecules becomes more refined and allows us to better use this technique.
The role of x-ray crystallography in SBDD is to allow us to directly observe the interaction between the compound of interest and the target, by interacting the two and obtaining the structure. This process is iterative. The information from this structure can aid in making new changes to the drug and then viewing the interaction between the new compound and the target. This can greatly increase the efficiency in making new and effective drugs by reducing the element of chance in drug design.
There are several commercially available drugs that have been designed using SBDD and more are in development. Tamiflu (influenza), Gleevec (leukemia) and Crixivan (AIDS) are all examples of drugs designed using structural information. Future drug development will increasingly depend on the knowledge and the design of new compounds instead of relying on luck to find a useful drug among compounds that already exist.
Traditional drug screening involves physically testing a large library of compounds (thousands or millions) against a target of interest and then using the 'hits', the compounds that show desired activity, as a template to produce better compounds. This process is expensive and time consuming, and is consequently only available to large organizations capable of funding such research. Virtual Screening (VS) allows a much larger number of researchers the ability to screen libraries of compounds without the expense of a physical compound library.
Compounds are tested in silico, that is, fit into the active site of the enzyme target by a computer according to criteria set by the researcher. By using existing knowledge about the target and it's interactions and other known physical properties of the target, VS allows researchers to pre-select compounds which show some potential interaction with a target. This saves time and decreases the cost associated with developing a new compound.