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In 2013 I switched to protein design. Based on my experience with protein structure prediction I was able to develop a fast, robust and completely computational method for protein design. My work has transformed protein design from a state where <1% designs pass structure prediction (a key check of protein viability) to a state where approximately 50% pass. This improved design strategy has led to a very high success rate with 44 out of 83 proteins ordered having the expected structure. [ ]. This general method will serve as the basis for design of functional de-novo proteins in the near future.

From 2011-2013 I worked on homology modeling. In homology modeling hybridizing homologs outperforms a wider search of conformation space near the homologs.  [unpublished work & ]. During these years I implemented the homolog identification and alignment system on http://robetta.bakerlab.org/ and conducted work on how to explore a wide region of conformation space in the vicinity of homologs.

From 2005-2011 I researched de-novo structure prediction and new methods for optimization [ ,, ]. Much of this work remains unpublished due to negligible RMSD improvements(even though energy was significantly improved). As of today only 8% of monomeric proteins < 120 amino acids can be predicted < 3 RMSD [unpublished work].

Brunette, T., & Brock, O. (2008). Guiding conformation space search with an all-atom energy potential. Proteins, 73(4), 958–972. https://doi.org/10.1002/prot.22123
Thyme, S. B., Song, Y., Brunette, T., Szeto, M. D., Kusak, L., Bradley, P., & Baker, D. (2014). Massively parallel determination and modeling of endonuclease substrate specificity. Nucleic Acids Research, 42(22), 13839–13852. https://doi.org/10.1093/nar/gku1096
Song, Y., DiMaio, F., Wang, R. Y.-R., Kim, D., Miles, C., Brunette, T., … Baker, D. (2013). High-resolution comparative modeling with RosettaCM. Structure (London, England: 1993), 21(10), 1735–1742. https://doi.org/10.1016/j.str.2013.08.005
Brunette, T., & Brock, O. (2005). Improving protein structure prediction with model-based search. Bioinformatics (Oxford, England), 21 Suppl 1, i66-74. https://doi.org/10.1093/bioinformatics/bti1029
Brunette*, T., Parmeggiani*, F., Po-Ssu*, H., Bhabha, G., Ekiert, D., Tsutakawa, S., … Baker, D. (2015). Exploring the repeat protein universe through computational protein design. Nature - Accepted - To Be Published.
Brunette, T. (2011, January 1). Adaptive balancing of exploitation with exploration to improve protein structure prediction. Retrieved from http://scholarworks.umass.edu/dissertations/AAI3461991/
Sweeney, J., Brunette, T., Yang, Y., & Grupen, R. (2002). Coordinated teams of reactive mobile platforms. Robotics and Automation, (ICRA’02). Retrieved from http://www.dtic.mil/cgi-bin/GetTRDoc?AD=ADA439657