Cafiero -- Theoretical and Computational Chemistry
Spring, 2009: Caroline Lee (11), Michelle Shroyer (11) and Hunter Utkov (10); not pictured: Maura Livengood(10), Emily Kee(09), Erin Carter (12), and Liz Jeans (11).
See Former Theoretical Chemistry Group member Karina Van Sickle as a Faces of Rhodes!
Current Theoretical Chemistry group members
Theoretical Chemistry Group Alumnae
Former Group Pictures
Ligand / Protein Binding
Much of our recent work has focused on the weak interactions between ring-shaped molecules. These ring-shaped molecules are very stable in the body and thus our physiology uses them in many ways. Most recently we have focused on the interactions between statin-type cholesterol-lowering drug molecules and their target in the body, an enzyme called HMG-Coenzyme-A reductase. The statin drugs work by finding the HMG Co-A reductase enzymes and fitting into their active site, thus blocking the body’s ability to produce more cholesterol. Both the statin drugs and the enzyme that they target contain the ring-shaped molecules we routinely study, and we have focused our efforts on tailoring these ring molecules so that the statin drugs will bind to the enzyme more tightly, thereby improving the effectiveness of the drug.
Our most recent work involves studying the interaction of a model intercalant molecule with small portions of DNA. We hope to identify what portions of DNA an intercalant molecule is most likely to stick to and we hope to characterize and quantify this interaction. This work can help in developing new chemotherapies to treat cancer more effectively.
Left: The enzyme Tyrosine hydroxylase; Right: Meghan Hofto (07) and Jessica Cross (08), with our computer, Devastator
Models for aromatic binding
In order to perform theoretical work on enzymes and biomolecules, we need good quantum mechanical methods that work well for these types of systems. We study these methods for the purpose of evaluating which ones are best for biological applications. Some of our recent work on these model systems has provided some interesting insight into the ability of molecules to wedge themselves in between the rungs in DNA. These molecules that disrupt DNA are called intercalants, and we have evaluated a suite of 15 molecules for intercalation ability.
Left: Electrostatic potential map of two benzene molecule bound together; Right: Lori Culberson (08) and Karina Van Sickle (08)
Current Students in the Theoretical chemistry group
Hunter Utkov, 2010
Projects: Hunter is working on developing statin-drug analogues with better enzyme-binding characteristics. Specifically, she is investigating the van der Waals interactions which bind the tail of HMG-CoA to the enzyme (HMG coA reductase) active site and evaluating the feasibility of using these interactions with existing statin drugs.
Conference presentations:
1. American Chemical Society National Conference, March 2009 (Salt Lake City, Utah) "Functional group based design of novel cholesterol moderating drugs using Ab Initio and DFT methods."
2. 13th International Congress of Quantum Chemistry, June 2009 (Helsinki, Finland) "Functional group based design of novel cholesterol moderating drugs using Ab Initio and DFT methods."
Laura Hofto, 2010
Projects: Laura is working on the design and application on novel 2-electron density based DFT methods to the problems of protein-ligand binding and ligand-nucleic acid binding.
Publications:
1. L. R. Hofto, K. Van Sickle, and M. Cafiero, “Evaluation of sandwich-type electronic interactions in fourteen polyaromatic molecules.” Int. J. Quantum Chem., DOI: 10.1002/qua.21426.
2. L.R. Hofto, M.E. Hofto, J.N. Cross, and M. Cafiero, “Using simple molecular orbital calculations to predict disease: fast DFT methods applied to enzymes implicated in PKU, Parkinson’s diseas, and obsessive compulsive disorder.” AIP Conf. Proc., 940, 127-136 (2007).
3. L.R. Hofto, C.E. Lee, and M.Cafiero “Scaling gradient dependant corrections to LSDA DFT methods for aromatic interactions: applications to Tryptophan hydroxylase” accepted, J. Comp. Chem.
Conference presentations:
1. Complife, October 2007 (Utretch, The Netherlands) "Using simple molecular orbital calculations to predict disease."
2. Mercury 2007 Conference, August 2007 (Clinton, NY) "Novel Density Functional Theory methods for describing Dispersion Interactions."
3. American Chemical Society National Conference, March 2008 (New Orleans, La) "Evaluation of novel DFT methods for dispersion-like forces in protein-ligand systems."
4. ESPA 2008, September 2008 (Palma de Mallorca, Spain) "Protein-Ligand Interaction Energies in Tryptophan Hydroxylase and Amino Acid Decarboxylase: Implications for the Production of Serotonin."
Caroline Lee, 2011
Projects: Caroline is working on DFT methods for studying mutations in amino acid decarboxylase.
Publications:
1. L.R. Hofto, C. E. Lee, and M.Cafiero “Scaling gradient dependant corrections to LSDA DFT methods for aromatic interactions: applications to Tryptophan hydroxylase” accepted, J. Comp. Chem.
Conference presentations:
1. American Chemical Society National Conference, March 2008 (New Orleans, La) "Evaluation of novel DFT methods for dispersion-like forces in protein-ligand systems."
2. ESPA 2008, September 2008 (Palma de Mallorca, Spain) "Protein-Ligand Interaction Energies in Tryptophan Hydroxylase and Amino Acid Decarboxylase: Implications for the Production of Serotonin."
3. American Chemical Society National Conference, March 2009 (Salt Lake City, Utah) "Dispersion and induction forces in serotonin synthesis: DFT and ab initio results."
Michelle Shroyer, 2011
Projects: Michelle is working on analysis of binding of intercalant molecules in DNA. Specifically, she is modelling three-molecule clusters consisting of two DNA bases surrounding a model intercalant in order to determine the likely locations and types of DNA deformations caused by the intercalant.
Publications:
1. K. Van Sickle, M. C. Shroyer, and M. Cafiero, “The effect of aromaticity and bond conjugation on dispersion-like forces between singly substituted six-membered carbon rings.” Submitted, J. Phys. Chem. A.
Erin Carter, 2012
Projects: Erin is working on charge migration in aromatic rings based on substituents and applications to aromatic binding in proteins; specifically, the binding of nicotine to AChBP
Publications:
1. E. A. Kee, M. C. Livengood, E. E. Carter, M. L. McKenna, and M. Cafiero, “Aromatic Interactions in the Binding of Ligands to HMGCoA Reductase.” Submitted, J. Phys. Chem. B.
Conference presentations:
1.Mercury 2009 Conference, August 2009 (Clinton, NY)
Liz Jeans, 2011
Projects: Liz is studying the intermolecular forces between aromatic rings and borazine rings (6-membered rings of alternating nitrogen and boron). Borazine has different binding properties than carbon-analogue rings and may be useful in biochemical applications.
Alumnae of the Theoretical Chemistry group
Meghan Hofto, 2007 (Honors Research) - Currently attending University of Tennessee Medical School
Publications:
1. M. E. Hofto , A. Godfrey_Kittle, and M. Cafiero " Substrate-Protein interaction energy in the enzyme Phenylalanine Hydroxylase: DFT and ab initio Results ", THEOCHEM, doi:10.1016/j.theochem.2007.01.023
2. M. E. Hofto, J.N. Cross, and M. Cafiero "Interaction energies between tetrahydrobiopterin analogues and phenylalanine residues in tyrosine hydroxylase and phenylalanine hydroxylase.", Physical Chemistry B, DOI: 10.1021/jp072518w.
Conference presentations:
1. American Chemical Society National Meeting, March 2007 (Chicago, Il), Poster: “Protein/ligand interactions in Phenylalanine Hydroxylase: DFT and ab initio results.”
2. Conference on Current Trends in Computational Chemistry, November 2006 (Jackson, MS), Poster: “Density Functional Theory methods for dispersion interactions in proteins.”
Lori Culberson, 2008 - Cuurenly attending the University of Arizona for graduate school in Chemistry
Publications:
1.K. Van Sickle, L.M. Culberson, J.L. Holzmacher and M. Cafiero, “Evaluation of Density Functional Theory methods for the electronic interactions between indole and substituted benzene: Applications to Horseradish Peroxidase”. Int. J. Quantum Chem. 107, 1523-1531 (2007).
Conference presentations:
1. Mercury 2007 Conference, August 2007 (Clinton, NY) "Novel Density Functional Theory methods for describing Dispersion Interactions."
2. CCTCC 2007, November 2007 (Jackson, Ms) “Two-electron DFT methods for modeling dispersion interactions”
3. American Chemical Society National Conference, March 2008 (New Orleans, La) “Two-electron DFT methods for modeling dispersion interactions”
Jessica Cross, 2008 - Currently attending University of Alaska, Fairbanks for graduate school in Chemistry
Publications:
1. M. E. Hofto, J.N. Cross, and M. Cafiero "Interaction energies between tetrahydrobiopterin analogues and phenylalanine residues in tyrosine hydroxylase and phenylalanine hydroxylase.", Physical Chemistry B, DOI: 10.1021/jp072518w .
2. Hofto, L.R., Hofto, M.E., Cross, J.N., and Cafiero, M., “Using simple molecular orbital calculations to predict disease: fast DFT methods applied to enzymes implicated in PKU, Parkinson’s diseas, and obsessive compulsive disorder.” AIP Conf. Proc., 940, 127-136 (2007).
Conference presentations:
1. American Chemical Society National Meeting, March 2007 (Chicago, Il), Poster: “Protein/ligand interactions in Phenylalanine Hydroxylase: DFT and ab initio results.”
2. Conference on Current Trends in Computational Chemistry, November 2006 (Jackson, MS), Poster: “Density Functional Theory methods for dispersion interactions in proteins.”
3. CCTCC 2007, November 2007 (Jackson, Ms) “Can DFT dissolv CO2 in water?"
4. American Chemical Society National Conference, March 2008 (New Orleans, La) “Can DFT dissolve CO2 in water?”
Karina Van Sickle, 2008 - Currently attending Univeristy of Memphis
Publications:
1. L. R. Hofto, K. Van Sickle, and M. Cafiero, “Evaluation of sandwich-type electronic interactions in fourteen polyaromatic molecules.” Int. J. Quantum Chem., DOI: 10.1002/qua.21426.
2.K. Van Sickle, L.M. Culberson, J.L. Holzmacher and M. Cafiero, “Evaluation of Density Functional Theory methods for the electronic interactions between indole and substituted benzene: Applications to Horseradish Peroxidase”. Int. J. Quantum Chem. 107, 1523-1531 (2007).
3. K. Van Sickle, and M. Cafiero, “The effect of aromaticity and bond conjugation on dispersion-like forces between singly substituted six-membered carbon rings.” Submitted, J. Phys. Chem. A.
Group Pictures
Summer, 2007: (Left to right) Karina Van Sickle (08), Lori Culberson (08), Krisitn Pugh (10).
Fall, 2006: (Left to right) Alex Woods (09), Jessica Cross (08), Meghan Hofto (07), Karina Van Sickle (08), and Lori Culberson (08).
Summer, 2008: (Left to right) Emily Kee (09) and Maura Livengood (10).
Fall, 2007: Front: Laura Hofto (10), Back: Jessica Cross (08), Lori Culberson(08), Mauricio Cafiero, Megan Mckenna (08). Not pictured: Karina Van Sickle (08).
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