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W. David Wilson

Regents Professor / Biophysical
Education

B.S. 1966, University of North Carolina, Chemistry
Ph.D. 1970, Purdue University, Biophysical Chemistry

Specializations

Biophysical Chemistry

Biography

Research Interest:

Molecular Modeling results for a novel synthetic compound from the Boykin Lab docked into a mixed base pair DNA sequence sequence. A new design concept for broad recognition of genomic sequences.

Molecular Modeling results for a novel synthetic compound from the Boykin Lab docked into a mixed base pair DNA sequence sequence. A new design concept for broad recognition of genomic sequences.

Research in the Wilson laboratory is focused on nucleic acid structure and the interactions of nucleic acids with molecules that range from small synthetic compounds to large proteins, such as transcription factors, that are the proteins responsible for orchestrated, temporal expression of specific genes.  We wish to establish models for the molecular basis that underlies the interaction functional mechanisms for protein-DNA complexes, including the influence of bound water molecules and solution salt concentration. A second major project in the Wilson Group involves design and evaluation of the DNA interactions of small molecules that can enter cells and modify a targeted function in a programmed manner. These projects converge at the DNA binding sites of transcription factors and our goal of modifying, either enhancing or inhibiting, the affinity of these critical gene control regulators with DNA.  In order to successfully conduct this design effort we use a range of solution biophysical, structural and computation methods. The compounds that are needed must be able to specifically recognize DNA sequences that contain different numbers in a different order of AT and GC base pairs in a double helix.  We are in the first stages of this project that is a collaboration with Professor David Boykin, whose group carries out the compound synthetic research. We use a range of very powerful tools in the research from absorption, circular dichroism, fluorescence and NMR spectroscopies, mass spectrometry, biosensor surface plasmon resonance for compound binding constants, kinetics and cooperativity in molecular interactions, and microcalorimetry for development of a full understanding of the thermodynamics of biomolecular interactions.

We are also involved in a number of collaborative efforts to identify and characterize compounds that can bind to the DNA quadruplex that forms from the telomere sequence at the ends of human chromosomes or in some oncogene promoter regions. Compounds that bind to the telomere quadruplex have the ability to inhibit the telomerase enzyme that extends the telomere to maintain the viability of rapidly dividing cells. Since many human cancers require telomerase activity, inhibition of this enzyme is a very attractive method to selectively attack cancer cells. A number of very promising compounds have been discovered and are now under study. At the same time, we are searching for general principles that can be used in the design of quadruplex targeting compounds.

Publications

Representative Publications

  1. “Molecular Basis For Sequence-Dependent Induced DNA Bending.” M. Rettig, M. Germann, S. Wang, W. D. Wilson, ChemBioChem 14, 323-331 (2013).
  2. “Probing The Electrostatics And Pharmacologic Modulation Of Sequence-Specific Binding By The DNA-Binding Domain Of The ETS-Family Transcription Factor PU.1: A Binding Affinity And Kinetics Investigation.” Manoj Munde, Gregory M. K. Poon, W. David Wilson, J. Mol. Biol. 425, 1655-1669 (2013).
  3. “Different Thermodynamic Signatures For DNA Minor Groove Binding With Changes In Salt Concentration And Temperature.” Shuo Wang, Arvind Kumar, Karl Aston, Binh Nguyen, James K. Bashkin, David W. Boykin, W. David Wilson, Chem. Commun. 49, 8543-8545 (2013).
  4. “Binding To The DNA Minor Groove By Heterocyclic Dications: From AT Specific Monomers To GC Recognition With Dimers.” Rupesh Nanjunda and W. David Wilson, Current Protocols in Nucleic Acid Chemistry, Chapter 8: Unit 8.8 (2012).
  5. “Designed Compounds For Recognition Of 10 Base Pairs Of DNA With Two AT Binding Sites.” Y. Liu, Y. Chai, A. Kumar, R. R. Tidwell, D. W. Boykin, W. D. Wilson, J. Am. Chem. Soc. 134, 5290-5299 (2012).