The Topology of Peptide/Protein Interaction Space

Arizona State University, Scottsdale AZ

Investigators

Abstract

Recent advances in high throughput, array-based synthesis of peptides make it possible to generate a detailed map of peptide/protein interaction space. Such a map will be created for the interaction of 17-amino acid peptides with four specific proteins. This map will help define in a precise way how the primary structure (amino acid sequence) of a peptide relates to its ability to bind a specific protein. This is of fundamental importance to our understanding of molecular recognition (the ability of one molecule to specifically recognize another). Molecular recognition is a key element in all almost aspects of biochemistry (binding, catalysis, etc.) and an understanding of how to predict molecular recognition based on the structure of a molecule will empower myriad practical applications. The technology that will be used to accomplish this is in many respects revolutionary. It has grown out of a type of synthetic approach developed by the pioneers of the DNA chip industry. DNA chips are made by synthesizing up to millions of different DNA oligonucleotides at a time on a glass slide in an ordered array. Intel has adapted and improved this process so that it is compatible with their platform for electronic chip manufacturing. This makes it possible to pattern the production of peptides on a silicon wafer with a resolution approaching that of patterned electronic components (on the order of two hundred nanometers). The high density allows the creation of libraries with up to hundreds of millions of peptides. It also allows the fabrication of peptides directly on electronic devices which will open the door for direct electronic/biochemical interfaces. Broader Impacts The development of this technology has far reaching implications for chemistry, biochemistry and biology. There is a huge interest in peptide ligands as parts of biosensor systems used in environmental and industrial monitoring and as specific molecular probes for fundamental biological research. Beyond that, the chemistry of this approach is much more general than just peptide chemistry. In fact, a large variety of molecules can be made on these surfaces, allowing the exploration of many other chemical spaces besides peptide space. This has clear implications for the development of new catalysts, the optimization of chemical reactions, the development of new materials, and molecular interfaces with electronics devices. This project will also involve a postdoctoral fellow, advancing that individual's career and preparing him/her as a leader in this developing field. In addition, the postdoc will mentor a high school teacher/high school student pair during the summer, passing on enthusiasm for a general understanding of science.