• 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

• Classical, force-field based Molecular dynamics• 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

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

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?

Collaborators and Group members

Salsbury Group

Prof Freddie Salsbury

Lacra Negureanu, Postdoc

Yan Lu, Postdoc

Xinfu Lu, Grad Student

Ryan Godwin, 1st 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.eduhttp://bob.olin.wfu.edu/~webContact: salsbufr@wfu.eduhttp://bob.olin.wfu.edu/~web