Mission statement: Our goal is to understand and be able to predict the physico-chemical mechanisms by which molecules,
including mutagens, carcinogens, drugs, and drug candidates, interact with DNA molecules. The ultimate goals are to
achieve a molecular-level understanding of carcinogenesis, to help develop strategies that prevent carcinogenesis, and to
help develop better therapies.
Our DNA molecules encode in their base sequence the information required for the cells to produce proteins.
Proteins perform all cell functions and help maintain the integrity of our cells.
Since cells are part of organs, organ systems, and the entire human organism, we can see how DNA, a molecule, can affect human organisms.
If our DNA molecules encode wrong information in critical places, then our cells will not be able to produce fully functional proteins,
which means that our cells will not be able to perform their function as part of organs, resulting in a problem of the organism, at the macroscopic level.
One of our projects is to study the binding of small molecules to DNA, such as carcinogen binding to DNA.
Our DNA molecules are constantly interacting physically and chemically with small molecules that are in the vicinity.
For example a carcinogen can physically bind to DNA in the grooves (minor or major) or intercalate between two base pairs.
This physical interaction can be easily reversed and thus it does not constitute permanent damage to DNA.
The physical binding of a small molecule to DNA can interfere however with how proteins interact with DNA molecules.
A carcinogen however, can also form a chemical bond with DNA, which is DNA damage.
This DNA damage can lead to mutations that may significantly affect the somatic cells, organs, tissues, and subsequently the organism.
Mutations in germ cells can result in birth defects and early childhood cancers.
For more information on cancer please see the presentation from the National Cancer Institute about
Our project is to understand at the molecular level these interactions that lead to diseases
We have presented our work thus far to the National Meeting of the American Chemical Society at Indianapolis in September 2013,
and to the locally organized Drury Science Undergraduate Research Symposium. On February 2014 we published our study of how a tobacco smoke carcinogen
interacts with exon 1 of a proto-oncogene, and a few months later we published another article on using a computational docking method to predict the
physical binding of small molecules to DNA.
Presentations and Publications
- Utilization of a predictive computational methodology to determine non-covalent ligand-DNA binding sites: Validation and application to B[b]F-TP53,
Alan JQ Greene and Christos Deligkaris, 2014 Midwest Regional Meeting of the American Chemical Society, Columbia, MO (November 2014)
- Inclusion of empirical entropic contributions to binding free energy of DNA-ligand systems during docking,
G.W. C. McElfresh and Christos Deligkaris, 2014 Midwest Regional Meeting of the American Chemical Society, Columbia, MO (November 2014)
- Validation of a computational docking methodology to identify the non-covalent binding site of ligands to DNA, Christos Deligkaris, Anthony Thomas Ascone, Kevin Joseph Sweeney, Alan Jonathan Quentin Greene, Mol. BioSyst. 2014
- Comprehensive validation of a computational docking methodology to identify the noncovalent binding site of a ligand to DNA, Christos Deligkaris, Anthony Thomas Ascone,
Kevin Joseph Sweeney, American Chemical Society National Meeting, Indianapolis, Fall 2013
- Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene, Phys. Chem. Chem. Phys. 2014
- Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene, Jorge H. Rodriguez and Christos Deligkaris,
APS March Meeting, 2013, Baltimore, Maryland (March 2013)
- A Computational Study of the Non-covalent Interactions between the K-ras Gene and some (BPDE and Acrolein) Carcinogens, Christos Deligkaris and Jorge H. Rodriguez,
52nd Annual Meeting of the Biophysical Society, Long Beach, California (February 2008)