Overview of our Research Projects

We work mainly on computational biophysics and biochemistry projects. That is, we use computers and computer programs to study the physico-chemical interactions of biological molecules that are implicated in diseases, such as cancer. With simulations we can get insight of biophysical and biochemical processes at the molecular level that no experiment can give (at least not easily).

In addition, we are also working on computational physics projects, such as the prediction of the motion of a pitched baseball/softball, and the prediction of the motion of water drops around knitting needles in space.

Read this very nice article that appeared in Springfield's News-Leader about the research two group members (Deborah Peana and Breanna Tuhlei) are doing!

Small molecule (carcinogens, drugs) binding to DNA

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 Understanding Cancer. 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

Binding of glycosaminoglycans to proteins

Mission statement: Our goal is to understand and be able to predict the physico-chemical mechanisms by which heparin and heparan sulfate interact with proteins. The ultimate goals are to achieve a molecular-level understanding of the role heparin and heparan sulfate play in metastasis and other diseases, to help develop strategies that prevent these events, and to help develop better therapies.

We study computationally the binding of a particular class of small molecules, namely glycosaminoglycans, to various proteins. Heparin and heparan sulphate are complex polysaccharides (sugars) ubiquitously found on all mammalian cell surfaces and within the extracellular matrix. They are members of the glycosaminoglycan family and bind selectively to a variety of proteins. For example, glycosaminoglycans bind to chemokines and modulate their activities, by creating a chemokine concentration gradient, or by promoting/inhibiting their interactions with the chemokine receptors. Glycosaminoglycans, and in particular heparin and heparan sulfate, therefore play important roles in many physiological and pathological processes including angiogenesis, anticoagulation, and metastasis. We are studying the physical interactions between heparin/heparan sulfate and various proteins in order to understand at the molecular level the biological processes that lead to diseases.

We have presented our work thus far at the National Meeting of the American Chemical Society in New Orleans in March 2013 (Brea Lombardo won an ACS award for her presentation!), the Midwest Regional Meeting of the American Chemical Society in October 2013, as well as the locally organized Drury Science Undergraduate Research Symposium.

Presentations and Publications

  • Validation of a computational methodology to identify the noncovalent binding site of heparin oligosaccharides to proteins, Deborah Peana, Cynthia B. Lombardo, Christos Deligkaris, ACS 2013 Midwest Regional Meeting
  • Binding of heparin oligosaccharides to proteins: Validating a computational methodology, Cynthia B. Lombardo, Christos Deligkaris, American Chemical Society National Meeting, New Orleans, Spring 2013

Preventing DNA damage from carcinogens (chemoprevention)

Mission statement: Our goal is to understand and be able to predict the physico-chemical mechanism with which pharmacological agents scavenge carcinogens. The ultimate goal is to design cancer chemopreventive molecules that can scavenge carcinogens originating from various environmental sources.

According to the World Health Organization, world-wide cancer incidence will continue to rise. Cancer chemoprevention is the use of pharmacological agents for preventing the incidence of cancer. Remember that cancer is a state, whereas carcinogenesis is the 20-year-long (approximately) process that leads to the state of cancer. With chemoprevention, we can (ideally) stop the progress of carcinogenesis, before cancer is manifested at the macroscopic level.

We are studying the physico-chemical interactions of a tobacco smoke carcinogen (BPDE), and a molecule commonfly found in berries and tea (ellagic acid). Ellagic acid reacts with the carcinogen extremely rapidly, which prevents DNA damage from BPDE. We want to understand the mechanism behind the scavenging ability of ellagic acid and in the future design molecules, potential drug candidates, that could scavenge different carcinogens.

Predicting the motion of a pitched baseball/softball

When a ball leaves the hand of the pitcher it interact with air molecules (contact interaction) and with the Earth (gravitational interaction). Due to the rotational motion of the ball (baseball or softball), the contact interaction with air molecules is fairly complicated. The contact force the air exerts on the ball can be broken in two components, which we call the air resistance and the Magnus component. This contact force has a significant impact on the motion of the ball, which is why it is so difficult for batters to hit a pitched ball. We are working on predicting computationally the motion of pitched baseballs and softballs.

Predicting the motion of water drops around knitting needles in space

An astronaut (Dr. Pettit) of the International Space Station recently did a very cool experiment. Dr. Pettit demonstrated how water drops can orbit a charged knitting needle in space, in the same way that our moon orbits the earth (the nature of the interaction is different in the two cases). We were motivated from this demonstration and we started working on computational predictions of the motion of water drops around charged knitting needles in space.

Improving implementations of a quantum mechanical theory (KS-DFT) for noncovalent interactions

Presentations and Publications

  • Correction to DFT interaction energies by an empirical dispersion term valid for a range of intermolecular distances, Phys. Chem. Chem. Phys.
  • Correction to DFT interaction energies by a dispersion term valid for a range of intermolecular distances: The DFT-DD methodology, Jorge H. Rodriguez, Christos Deligkaris, and Bennett Marsh, 246th National Meeting of the American Chemical Society, Indianapolis, IN (September 2013)
  • Correction to DFT Interaction Energies by an Empirical Dispersion Term Valid for a Range of Intermolecular Distances, Christos Deligkaris and Jorge H. Rodriguez, APS March Meeting, 2012, Boston, Massachusetts (March 2012)
  • Computation of Interaction Energies via Density Funtional Theory with Empirical van der Waals Corrections, Christos Deligkaris and Jorge H. Rodriguez, 238th National Meeting of the American Chemical Society, Washington, DC (August 2009)

Training the next generation of scientists

Mission statement: To engage undergraduate students in inquiries or investigations that make an original contribution to the field of computational biophysics/biochemistry and help them become professionals computational biophysicists/biochemists.

Presentations and Publications

  • Engaging undergraduates in computational biophysics/biochemistry research: predicting physical binding of small molecules to biomacromolecules, Christos Deligkaris, 2014 Gordon Research Conference in Physics Research & Education, Mount Holyoke College, South Hadley, MA