Folding Forum

Project Description:
Bryostatin is a marine natural product that shows promising and unique activity against several diseases (most notably, cancer, HIV/AIDS, and Alzheimer’s). Its main target, protein kinase C (PKC), is a signaling protein central to many cellular functions. In its active form, PKC binds its ligand and is associated with the membrane, but we currently lack structural information about this complex in its membrane microenvironment. The simulations performed on FAH will help to provide a structure to the PKC-ligand-membrane complex. The structure and dynamics of this complex would allow us to understand bryostatin’s binding mode and thus how to modify and tune its structure to improve function or even create new functions as needed for new therapies in the clinic.

Project Description:
The Src family protein tyrosine kinases are enzymes that play key roles in transducing cellular signals regulating cell growth, differentiation, proliferation, migration and survival. These enzymes are responsible for diseases such as cancer in which the cells undergo uncontrolled differentiation. Crystallographic x-ray structures of human c-Src in the inactive and active conformation allow clear structural distinctions to be drawn between the inactive and active states. Those x-ray structures, though rich in information about the two end-points of the activation event...

gbowman wrote:We don't have anything on immune deficiency right now, but are discussing some new collaborations on that topic. More on Alzheimer's coming soon.

gbowman wrote:I believe the work on Bryostatin and Src kinase are both "complete" in the sense that the researchers answered the questions they wanted to address, published the papers, and have now moved on to the next stages of their careers. I'm optimistic the work that has been done will inspire new projects. Certainly there are a number of projects on kinases already and we're looking into doing more related to Bryostatin.