Principal Investigator Amy Keating
We apply a wide range of computational tools to the analysis of protein interactions, including structure-based modeling, sequence analysis and machine learning. Some projects in the lab are focused on developing or improving computational methods, and a recent exciting advance was our collaboration with the Ceder group (MIT Materials Science) to adapt the technique of cluster expansion for use in protein modeling. Cluster expansion allows the energy of a protein folded into a certain structure to be expressed directly as a function of sequence. The approach brings dramatic speed-ups to modeling calculations while retaining many of the benefits of physical, structure-based approaches. We have also explored many methodological aspects of computational protein design (including the use of cluster expansion in design).
Computational modeling of structure can provide insights into determinants of protein interaction specificity, and structure-based design is becoming a powerful tool for generating new molecules. We are developing tools to facilitate the use of structure-based methods for designing interaction specificity.