----------------------------------------------------------------------- BIOINFORMATICS COLLOQUIUM College of Science George Mason University ----------------------------------------------------------------------- Engineering Proteins for Enhanced Activity Steven Fairchild Mitre Abstract: The ability to computationally re-engineer proteins for enhanced binding activity would enable rapid development of therapeutic agents. For example, enzymes could be engineered to have increased affinity towards a reaction's transition state. This would facilitate the development of enzymes with increased and/or novel catalytic activity. The software would also enable the construction of proteins that have improved binding characteristics towards target molecules. These proteins could then be utilized for bio-remediation purposes or as signaling molecules that elicit specific cellular responses. Along these lines, our group has developed a protein design pipeline (PDP) that facilitates computational re-engineering of protein structures to enhance binding capabilities. The software starts with a known protein structure and a list of residues that constitute the active/binding site. The software then utilizes a genetic algorithm to detect optimal mutations for improving binding activity towards a target molecule (either a reaction's high-energy transition state or a particular molecule of interest). Ultimately, the PDP is shown to work well at optimally re-engineering protein structures to have novel functionality.