Protein Complex Discovery
Protein complexes are physically associated proteins that carry out many of the cell's essential functions. A fundamental question in biology is to understand how proteins organize themselves into these functional molecular machines. I build computational methods which analyze and integrate large scale protein interaction data towards the aim of assemblying the set of all protein complexes. These methods identify novel protein complexes as well as novel subunits of known complexes which allows us to ask additional question about how protein complexes arise through evolution as well as identify novel disease gene candidates and functions for unannotated genes.
Protein Interaction / Complex Structural Modeling
The three dimensional structure of protein complexes determines its function in the cell. Knowledge of the structure of complexes allows for the mechanistic understanding of its function and provides clues as to why certain mutations disrupt its function. I work on computational methods that model the three dimensional structure of complexes and their subunits. I pull from several fields of research to achieve this aim including proteomics correlation analysis, structure prediction and co-evolution analysis.
(Wan, Borgeson et al. Nature 2015)
Protein Interaction Inhibition
Proteins rarely work in isolation but rather physically associate with other proteins in order to carry out their cellular functions. Large molecular machines are often required for a function to be carried out but other physical associations act as regulators that restrict functions to be carried out at specific times and locations in the cell. I develop computational tools to design small molecules that mimic a protein's binding partner towards the aim of disrupting the protein's interaction. A major goal of this project is to create algorithms which can sample a molecule's conformational and chemical space to find high affinity binders to the target protein of interest. The ability to modulate how functions are regulated is a powerful tool for inquiry into how the cell works but also can be used to correct a malfunctioning regulatory network in diseased cells such as cancer.
(Bullock Lao, Drew et al. JACS 2014)