CAREER: Combined Computational and Experimental Approaches for the Design of Protein-Protein Interactions

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Molecular self-assembly is the spontaneous association of molecules into stable, structurally well-defined complexes joined by noncovalent bonds. The objective of this CAREER project is to understand and ultimately control the forces that drive protein self-assembly. To achieve this aim, the PI will use an inverse approach that combines cutting-edge computational docking methods with advanced protein design algorithms to drive the self-assembly of previously monomeric proteins. The proteins will be computationally docked together and then treated as one where interfacial side chains are mutated and repacked in a manner analogous to the core of a well-folded protein. The goal is to select the specific amino acids that, upon mutation, will provide the physical chemical interactions that drive complex formation. To complement these efforts powerful experimental techniques will be employed that function to screen combinatorial libraries of mutant candidate proteins for those that bind target proteins with high affinity. This CAREER project will contribute to the development of the PI as a teacher-scholar as it incorporates educational programs for undergraduate, graduate, postgraduate and middle/high school students. In addition to the above research efforts a laboratory course is being developed that is meant to provide students with a firm understanding of the chemical and biological principles that underlie the emerging field of forensics science. The educational impact of this research is exemplified by the fact that the PI is working collaboratively with San Diego County agencies to develop a series of inquiry-based lab modules for a pilot program in which students from underserved areas explore basic methods used in forensic science. The merit of this educational aim is to instill in youth the lifelong desire to learn and thereby succeed.