My research efforts use computational methods to gain insights into biochemistry and atmospheric chemistry. My research group uses quantum chemistry, Monte Carlo, and molecular dynamics techniques to investigate the structure and function of molecules. The common theme throughout is the involvement of undergraduates in a productive and meaningful research experience.
Computational pKa Prediction
Using these methods requires a thorough understanding of solvation effects, and much of our basic work involves finding and learning how to use the best methods for incorporating solvation into traditional computational chemistry techniques. We have completed a systematic study of pKa calculations, funded by the American Chemistry Society (ACS), Petroleum Research Fund (PRF) and National Science Foundation (NSF), in order to learn how state-of-the-art methods can best be used to accurately predict deprotonation in aqueous solution.
We had drug design projects with funding from NIH, DOD, and Research Corporation, with an emphasis on breast cancer. Alpha-fetoprotein (AFP) is a protein produced by the fetal yolk sac and is presumed to act as a growth regulator during gestation. It is 591 amino acids long. It was discovered that high levels of circulating AFP in maternal serum decrease a woman’s risk of developing estrogen receptor positive (ER+) breast cancer later in life. It has recently been discovered that the peptide can be shortened to peptides as small as 4 amino acids long and still retain active breast cancer inhibition qualities. We have applied and demonstrated for the first time that replica exchange molecular dynamics (REMD) simulations can be used as a novel lead compound design tool. We have shown that a common conformation that is shared between the active linear 8-mer and cyclic 9-mer peptides of AFP is a conserved reverse beta-turn, and the smaller peptide analogs TOVNO, TPVNP, TOVN, and TPVN. These analogs inhibit estrogen-dependent cell growth in a mouse uterine growth assay, through interaction with a yet to be discovered key receptor, and inhibit human breast cancer in a mouse xenograft.
Structure and Properties of Water Clusters and Atmospheric Hydrates
We are also working on projects in atmospheric chemistry that focus on the role of water clusters. The aim is to locate the global and all relevant low lying local minima for each cluster.
Our sampling methods ensure that we have searched the large configurational space of hydrogen bonding networks available to these clusters and extracted the lowest energy configurations. Our quantum mechanical method of choice, MP2 is the most affordable yet very accurate method for studying non-covalently bonded systems like water clusters. The interplay between energy and entropy, the shapes and hydrogen bonding networks of the clusters are used to explain the growth patterns of the clusters. Ultimately, this information will be used to calculate cluster populations and nucleation rates that are compared with experiment rates of formation of aerosol particles.
Improved understanding of atmospheric aerosol formation would reduce the large uncertainty in the cooling effect of aerosols on the global radiation balance (see below) and refine global climate models.
IPCC WG1 4th Assessment Report, 2007