Maria Ildiko Zavodszky Maria Ildiko Zavodszky Research Associate Protein Structural Analysis and Design Laboratory Department of Biochemistry Michigan State University East Lansing, MI, 48824-1319 Biochemistry Building, Room 502 C

Professional Interests
We are developing a new method for modeling protein and ligand main-chain flexibility and show its ability to model fully flexible molecular recognition. Flexibility analysis of the target protein is performed using the graph-theoretic algorithm FIRST. The available conformational space of the predicted flexible regions is then explored with ROCK by random-walk sampling of the rotatable bonds. ROCK directly identifies and samples correlated motions by preserving the covalent and non-covalent bond-network of the protein. ROCK is unique in its ability to handle coupled ring systems and guarantees conformers with good stereochemistry without requiring expensive energy minimization. A representative set of the conformational ensemble generated this way can be used as targets for docking with SLIDE, which handles flexibility of protein and ligand side chains. ROCK can be used to model not only the flexibility of proteins but also that of large cyclic and polycyclic ligands. This combined approach is used to perform fully flexible docking. Several questions can be addressed using this approach: (1) How much flexibility of the interacting molecules is tolerated without hindering molecular recognition? (2) How does ligand binding change the flexibility of the protein? (3) How are flexibility changes propagated from one part of the protein to another? more flexible more rigid