Dr. Ryan Brenke
rbrenke [at] bu [dot] edu
The majority of my research is focused on computational method development and modeling of protein-protein and protein-small ligand interactions. These interactions are essential to biological processes. Computational modeling provides a potentially more efficient way of analyzing these interactions than can be attained by traditional experimental methods (such as X-ray crystallography) alone. As a core developer working with others in our lab, we have developed two primary software tools to study and predict protein-protein and protein-small ligand interactions: Piper/ClusPro and FTMap.
Piper uses Fast Fourier Transforms (FFTs) to efficiently sample a translational space using cross-correlations of simplified receptor and ligand energy functions. Together with rotation, a discretized 6-dimensional conformational space of the receptor and ligand proteins can be quickly sampled. The principal novelty of Piper is its simple representation of a complex energy function, which provides improved results compared to other methods.
In order to provide the docking community with access to the Piper docking tool, we have developed a server, ClusPro. ClusPro uses Piper as an initial stage docking algorithm along with a clustering algorithm in order to provide predicted docked models for a given pair of receptor and ligand proteins. ClusPro has been a top performer in CAPRI (Critical Assessment of PRediction of Interactions), a global experiment on the comparative evaluation of protein-protein docking for structure prediction.
Experimental studies suggest that the binding sites of proteins generally contain smaller regions that provide major contributions to the binding free energy - often termed “hot spot” regions. These regions are prime targets in drug design. We have developed the FTMap algorithm to determine these hot spots computationally rather than experimentally. FTMap has been applied to a number of different protein systems for which there is experimental data. According to these results, FTMap quickly and reliably identifies the hot spot regions of a protein binding site.