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• 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: [email protected]://bob.olin.wfu.edu/~webContact: [email protected]://bob.olin.wfu.edu/~web
