1. What are physically-reasonable methods for modeling macromolecules? How do we use analyze the data? How do we add more physics and mathematics into biological analysis? What is the relationship between protein dynamics and molecular function? How are “signals” transmitted within a protein and between proteins? How are these signals perturbed? How can this information be used in drug discovery? protein dynamics increasingly recognized as important to protein function and hence drug design and cancer biology What are physically-reasonable methods for modeling macromolecules? How do we use analyze the data? How do we add more physics and mathematics into biological analysis? What is the relationship between protein dynamics and molecular function? How are “signals” transmitted within a protein and between proteins? How are these signals perturbed? How can this information be used in drug discovery? protein dynamics increasingly recognized as important to protein function and hence drug design and cancer biology Protein Dynamics and Function: General themes

2. Classical, force-field based Molecular dynamics Main Tools Poisson-Boltzmann Equation and approximations Statistical analysis increasingly important Free energy landscape methods becoming important Some electronic structure calcs

3. Protein Dynamics and Function: Main systems Mismatch repair proteins: bifunctional (DNA repair vs cell death). Different long-range responses to binding events ; molecular signaling Target for chemotheraputic design Disease and dynamics associated mutants realistic system PRX: redox proteins; reduce peroxide, signaling proteins Activity depends on electrostatics; seem to show long-range communication within complexes; lots of data to understand from experiments Formation of assemblies important large-scale conformational changes Eglin C; small protein, well studied Exhibits communication across the protein as measured by many different measures (apo dynamics, dynamic/flexibility responses to mutation, folding) model system for method development

4. New systems: Zinc & DNA& proteins Zinc fingers: bind-DNA or proteins involved in regulation Target for chemotheraputic design What happens to their free energy landscape upon binding? Zinc-DNA interactions: How does Zinc affect modified DNA and binding of molecules to DNA? to modified DNA? Used to develop synergetic therapeutics and/or delivery devices?

5. Collaborators and Group members Salsbury Group Prof Freddie Salsbury Lacra Negureanu, Postdoc Yan Lu, Postdoc Xinfu Lu, Grad Student Ryan Godwin, 1 st year grad student Chris Stuart, (Part-time) grad student (with Bill Gmeiner) Collaborators Jacque Fetrow, CS/Physics Leslie Poole, Biochemistry Mark Welker, Chemistry Bruce King, Chemistry George Kulik, Cancer Biology William Gmeiner, Cancer Biology Karin Scarpinato, Georgia Southern Univ Contact: salsbufr@wfu.edusalsbufr@wfu.edu http://bob.olin.wfu.edu/~web Contact: salsbufr@wfu.edusalsbufr@wfu.edu http://bob.olin.wfu.edu/~web