Drug Discovery and Protein-Protein Interactions:
The completion of the sequencing of several genomes has revealed that the complexity of living organisms is not simply correlated with the number of proteins that they have. Rather, it is becoming increasingly clear that the major source of complexity depends on the many different interactions that proteins under Protein-protein interactions are critical for practically all cellular, signaling and regulatory pathways. The function of these pathways is the cause of many diseases including cancer and neurological diseases. Since damages and alterations in protein-protein interactions either cause or accelerate human diseases, the control or inhibition of the known interactions represents a prime target for drug discovery.
Protein-protein interactions occur at the protein surface. They are governed by the shape, chemical complementarity, and flexibility of the molecules involved as well as the environmental conditions. Consequently, interfaces are the ultimate regions where drugs should head. Understanding the details and principles of interfaces is of critical importance to develop a better strategy in drug design. Although the complexes of interacting proteins provide exciting and novel targets for potential new drugs, right now, very few drugs exist that inhibit protein-protein interactions. But, the Protein Data Bank, the international "public library" of solved protein structures from which scientists draw data, contains not just isolated proteins. but in many instances compounds of two or more interacting proteins. Since cellular signals are mediated by these protein-protein interactions, we want to know exactly who's interacting with whom. Often, the function of one protein can be deduced by studying the proteins with which it interacts.
Perhaps there are millions of these interactions, a seemingly intractable problem. But, the process is greatly accelerated if one has a computational method that helps pinpoint the sites on the interacting proteins that will help scientists discover their role in biochemical pathways. That's what our method aims to do. Using computers, we can start to see how the path fits together, how this enzyme interacts with that small molecule or functions in a cascade of cellular processes . We have implemented PRISM (Protein Interactions by Structural Matching), a web server that can be used to explore protein interfaces and predict protein-protein interactions protein interactions make it possible to target specific proteins more efficiently. Besides, to research against cancer is an intense ongoing project in our center. Combining computers with the experiments will be able to eventually lead to efficient drugs.
