Brian A. Kuhlman
Computational Protein Design / Protein-Protein Interactions / Structural Biology
We use a combination of computational and experimental methods to characterize and design proteins.
What is protein design? Most ambitiously it is the creation of novel proteins to perform useful tasks. At a more modest level it might be identifying amino acid mutations that enhance protein stability, alter binding specificity, or increase solubility.
How do we design proteins? We have developed a computer program that identifies low energy sequences for target structures or interfaces. In essence it is like solving a jigsaw puzzle. The pieces, in this case amino acids, must fit together so that there are no overlaps and little empty space. In addition, specific interactions like hydrogen bonding must be satisfied.
What are we currently designing? Our main focus is the design of protein-protein interfaces. We are developing methods for enhancing the affinity of existing interactions as well as creating new interactions from scratch. Potential uses for this technology include the creation of biosensors, probes to study cell biology, and therapeutics with enhanced activity.