Project Title: Combining Protein Design and Protein Dynamics to Target Conformational Flexibility in Molecular Recognition
This project is awarded under the Postdoctoral Research Fellowships in Biological Informatics Program for 2006. Maintaining effective molecular recognition between interacting proteins is of fundamental importance to all forms of cellular existence. The way in which proteins interact with one another is based on their ability to recognize their compatible partners in the dense and complex cellular environment. A major challenge in understanding protein recognition is to develop the methods that capture molecular basis of conformational changes upon binding. A combined approach will be followed, integrating available techniques in both protein design and protein dynamics to decipher the mechanisms of conformational transitions occurring upon protein-protein complexation. The project involves focused experimental projects concurrent with computational and theoretical work. The physical nature of interactions between monomers and their dynamics can therefore be dissected at the molecular level using methods of theoretical physics with experimental validations for computational predictions. It is the first time that large conformational changes are proposed to incorporate into protein design approaches to decipher mechanisms of protein conformational conversions upon complexation, at the interface between computing and experimentation.
The fellow will be working in the lab of Christopher Dobson at the University of Cambridge where she will enrich her background in theoretical physics, mathematics and computer science, with a firm knowledge of experimental biology and chemical information along with a close intertwining of experiment, theory, and computer simulation. The fellow will have the opportunity to contribute a portion of her research activities in community service through teaching, communicating, collaborating, and incorporating scientific computing methods to extend the existing, free PathSamp software package at Cambridge.
