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Molecular and Cellular Biosciences at Wake Forest University


Wake Forest University Graduate School » Molecular and Cellular Biosciences

Fred Salsbury, Ph.D.

Fred Salsbury, Ph.D.
The Salsbury group conducts research in computational molecular biophysics; broadly construed. Our research projects involve, in varying combinations, understanding the molecular physics behind biological function, applying physics-based tools to biomedically interesting systems, and improving the computational methods used in biological physics. Our particular biomedical interests lie in drug discovery and design, and in cancer biology.

 

32. D. Baiz, T. A. Pinder, S. Hassan, Y. Karpova, F. R. Salsbury Jr., M. E. Welker, and G. Kulik. Synthesis and Characterization of a Novel Prostate Cancer-Targeted PI3 Kinase Inhibitor Prodrug. Journal of Medicinal Chemistry Early view August 27 2012
31. F. R. Salsbury Jr, L. B Poole and J. S. Fetrow. Electrostatics of cysteine residues in proteins: Parameterization and validation of a simple model. Proteins Structure, Function and Bioinformatics. Early view Online Aug 21 2012
30. Structural and Electrostatic Asymmetry at the Active Site in Typical and Atypical Peroxiredoxin Dimers. Freddie R. Salsbury, Jr., Ye Yuan, Michael H. Knaggs, Leslie B. Poole, and Jacquelyn S. Fetrow JPCB 116:6832-6843 (2012)
29. L. Negureanu, and F. Salsbury Jr. The molecular origin of the MMR-dependent apoptosis pathway from dynamics analysis of MutSα-DNA complexes. Journal of Biomolecular Structure and Dynamics  30:(TBD) (2012) online June 18 2012
28. L. Negureanu, and F. Salsbury Jr.  Insights into protein - DNA interactions, stability and allosteric communications: a computational study of mutSα-DNA recognition complexes. Journal of Biomolecular Structure and Dynamics  29:756-76 (2012)
27. The Stability of a Model Substrate for Topoisomerase 1-Mediated DNA Religation Depends on the Presence of Mismatched Base Pairs William H. Gmeiner, Freddie Salsbury Jr.,Chris M. Olsen, and Luis A. Marky Journal of Nucleic Acids 2011/631372
26. S. Ghosh, F. Salsbury, D. Horita and W. Gmeiner, Zn2+ Selectively Stabilizes FdU-Substituted DNA Through a Unique Major Groove Binding Motif, Nucleic Acids Research  39:4490-98(2011)
25 N. R. Gassman J. E. Clodfelter A. K. McCauley, K. Bonin, F. R. Salsbury Jr and K. D. Scarpinato Cooperative Nuclear Localization Sequences Lend a Novel Role to the N-Terminal Region of MSH6 PLOS ONE 6(3): e17907 (2011)
24. F. R. Salsbury Jr., Molecular dynamics simulations of protein dynamics and their relevance to drug discovery Current Opinion in Pharmacology 10:738-744 (2010)
23. A. Vasilyeva, J. E. Clodfelter, M. J. Gorczynski, A. R. Gerardi, S. B. King, F. Salsbury and K. D. Scarpinato,” Parameters of Reserpine Analogs That Induce MSH2/MSH6-Dependent Cytotoxic Response” . J Nucleic Acids. 2010 Sep 13 (2010)
22. Y. Yuan, M. H. Knaggs, L. B. Poole, J. S. Fetrow and F. R. Salsbury Jr.,Conformational and oligomeric effects on the cysteine pKa of typaredoxin peroxidase, Journal of Biomolecular Structure and Dynamics 28 (1) 51-70 (2010)
21.Salsbury, FR Jr.,  Effects of Cisplatin Binding to DNA on the Dynamics of the E. coli MutS Dimer, Protein & Peptide Letters 17, 744-740 (2010)
20. F. R. Salsbury, M. W. Crowder, S. F. Kingsmore, J. J. A. Huntley, “Molecular dynamic simulations of the metallo-beta-lactamase from Bacteroides fragilis in presence and absence of a tight-binding inhibitor “ J. Mol. Model. (15) 133-145 (2009)
19. A. Vasilyeva, J. E. Clodfelter, B. Rector, T. Hollis, K. D. Scarpinato, and F. R. Salsbury, “Small molecule induction of MSH2-dependent cell death suggests a vital role of mismatch repair proteins in cell death.” DNA Repair, (8) 103-113 (2009)
18. F. R. Salsbury, S. T. Knutson, L. B. Poole and J. S. Fetrow, "Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid," Protein Science 17 299-312 (2008).
17. M. H. Knaggs, F. R. Salsbury, M. H. Edgell, J. S. Fetrow. Insights into CheY relaxation and relaxation derived from molecular dynamics simulations. Biophys J .2062-2079 (2007)
16. F. R. Salsbury, Jr, Clodfelter, J. E., Gentry, M. B., Hollis, T., Drotschmann, K., The molecular mechanism of DNA damage recognition by MutS homologs and its distinction from mismatch binding, Nucleic Acids Research, 34 (8) 2173-2185 (2006)
15. F. R. Salsbury, Jr,. Analysis of Errors in Still’s Equation for Macromolecular Electrostatic Solvation Energies, Molecular Physics, 104 (8) 1299-1309 (2006)
14. M.S. Lee, F. R. Salsbury, Jr., and M. A. Olson, An Efficient Hybrid Implicit/Explicit Solvent Method for Biomolecular Simulations that Uses A Generalized Born Reaction Field and Multigrid Enhancements, J Comput Chem. 25 (16) 1967-78 (2004).
13. M. S. Lee, F. R. Salsbury, Jr., and C. L. Brooks, III, Constant pH-molecular Dynamics using Continuous Titration Coordinate, Proteins: Structure, Function and Bioinformatics, 56 (4):738-752 (2004).
12. L. R. Thomas, A. Henson, J. C. Reed, F. R. Salsbury, Jr., and A. Thorburn, Direct Binding of FADD to the TRAIL Receptor DR5 is Regulated by the Death Effector Domain of FADD, J. Bio. Chem. 279, 31 (2004).
11. K. Drotschmann, R. P. Topping, J. E. Clodfelter, and F. R. Salsbury, Jr, Mutations in the Nucleotide-binding Domain of MutS Homologs Uncouple Cell Death from Cell Survival, DNA Repair, 3 (7):729-742 (2004).
10. F. R. Salsbury, Jr, W-G. Han, L. Noodleman and C.L. Brooks, III, Temperature-dependent behavior of protein-chromophore interactions: a theoretical study of a blue fluorescent antibody, Chemphyschem 4 (8): 848-855 (2003)
9. M. S. Lee, M. Feig, F. R. Salsbury, Jr., and C. L. Brooks, III, A New Analytical Approximation to the Standard Molecular Volume Definition and Its Application To Generalized Born Calculations, Journal of Computational Chemistry 24 (11): 1348-1356 (2003)
8. M.S. Lee, F. R. Salsbury, Jr, and C.L. Brooks, III, New and Novel Generalized Born Methods, J. Chem. Phys., 116 (24), 10606-10614 (2002).

7. F. R. Salsbury, Jr, M. F. Crowley, and C. L. Brooks, III, Modeling of the metallo-beta-lactamase from B. fragilis: Structural and dynamic effects of inhibitor binding, Proteins: Structure, Function, & Genetics 44(4) 448-459 (2001)

6. F. R. Salsbury, Jr., and R. A. Harris, On the origin of the magnetic field dependent quadrupolar splitting, J. Chem. Phys., 109 (19), 8338-8341 (1998).
5. R. A. Harris, and F. R. Salsbury, Jr., The exchange energy in a weak magnetic field, J. Chem. Phys., 109 (7), 2609-2613 (1998).
4. F. R. Salsbury, Jr., and R. A. Harris, Estimation of the Fermi Contact Contribution to the Xenon-Hydrogen and Xenon-Xenon Spin-Spin Coupling Constants, Mol. Phys. 94 (2), 307-312 (1998).
3. F. R. Salsbury, Jr., and R. A. Harris, A nonlocal current density functional for magnetic responses, J. Chem. Phys. 108 (15), 6102-6108 (1998).
2. F. R. Salsbury, Jr., and R. A. Harris, Hydrogen chemical shieldings: A magnetic field density functional approach, Chem. Phys. Lett., 279 (3,4), 247-251 (1997).
1. F. R. Salsbury, Jr., and R. A. Harris, The current in magnetic field density functional theory and its application to the chemical shielding and the magnetic susceptibility, J. Chem. Phys., 107 (18), 7350-7359 (1997).

 

Fred Salsbury's research focuses on computational biophysics and chemical physics. The members of Dr. Salsbury's group conduct research in computational molecular biophysics; broadly construed. Their research projects involve, in varying combinations, understanding the molecular physics behind biological function, improving the computational methods used in biological physics, and applying physics-based tools to systems of biomedical interest.

The underlying questions in molecular physics that drive the research in Dr. Salsbury's group are 1) how do proteins modulate molecular function through conformational change, 2) how does communication occurs within and between proteins and other macromolecues, and 3) how do molecular interactions, which are altered through conformational change, especially electrostatics, control function.

To address these questions, method development has to occur at times, especially to improve the range of problems addressable by computational physics. Dr. Salsbury is best-known for his work in developing Generalized Born solvation models, and implicit models of protonation, especially through the constant-PHMD method. Currently, Dr. Salsbury's group is more interested in developing tools to analyze and use simulations to better address the underlying questions of interest to his group, and to develop model protein systems for such questions

Dr. Salsbury's group is remarkable in that in addition to developing new methods, and studying model systems, a primary focus of their work is the study of macromolecules and macromolecular complexes of real practical and biological interest. Their recent focus has been on DNA repair proteins (MSH2/MSH6), redox proteins (PRXs) and metallo-beta-lactamases. Four specific areas are currently being explored, which focus on the underlying questions of interest to Dr. Salsbury's group : 1) using physics-based measures, especially electrostatics, to understand the molecular function of proteins with an eventual aim of improving bioinformatic tools by incorporating physical measures (PRXs); 2) studying conformational change and long-range communication in macromolecules (all projects) 3) understanding the molecular and physical basis for multifunctional proteins (MSH2/MSH6) and 3) developing theraupetics that act via conformational and functional selectivity, i.e., by selecting specific conformations that activate specific cellular functions (MSH2/MSH6). Most of this work is multidisciplinary and so Dr. Salsbury's group collaborates extensively with experimental biomedical researchers. This work is or has been funded by the NIH, NSF, TSI, and GAC.