Wayne State University

Aim Higher



College of Liberal Arts & Sciences
Department of Chemistry
Faculty Page
 
John Santalucia Jr.
Title Professor
Division Biochemistry (Physical/Theoretical/Computational)
Education B.S. Clarkson University, 1987
Ph.D. University of Rochester, 1991
NIH Postdoctoral Fellow, University of California, Berkeley, 1991-1994
Office Chem 485
Phone (313)577-0101
E-Mail
Group http://ozone3.chem.wayne.edu


There are three major research projects in our laboratory: 1) 3D structure prediction and analysis of RNA and DNA, 2) NMR structure determination of RNA with bound drugs and proteins, and 3) Nucleic acid-based nanotechnology.

Structural Bioinformatics of Nucleic Acids. The number of nucleic acid sequences in GenBank is increasing much faster than the 3D structures in the PDB. To address this problem, we are developing a suite of computational tools for nucleic acid sequence alignment, secondary structure prediction, de novo 3D structure prediction, 3D homology modeling (see figure), and structural analysis. Despite similarities to the protein folding problem, we have found that nucleic acids have unique characteristics that require new ideas. We are developing a new classical molecular simulation forcefield for nucleic acids and new conformational search methods. Important targets for structure prediction are the ribosomes from bacterial and eukaryotic pathogens. We are interested in developing methods that can automatically model both the RNA and protein components of ribosomes given the whole organism genome sequence. In addition, we are working to develop modeling methods for interactions of RNA with small molecules, which will enable virtual screening of new classes of drugs.

RNA Structure and Function. Our group uses NMR spectroscopy to solve atomic-resolution structures of biologically important RNAs. Comparison of the NMR structures of the wild-type and mutant sequences (collaboration with Dr. Philip Cunningham) allows for the determination of the key structural elements required for ribosome function. We are also studying the structure of RNA complexes with bound peptide ligands derived from library screening (collaboration with Dr. Christine Chow). The structures will be used to deduce the rules for RNA recognition and for rational design of peptidomimetics and refined drugs with improved pharmacokinetic properties.

Nucleic Acid Nanotechnology. An important goal of nanotechnology is to generate complex self-assembling molecular systems with predictable shape, dynamics, and catalytic properties. Both DNA and RNA have unique properties that make them well suited to nanotechnology applications. However, there has been a lack of understanding of 3D structure, molecular dynamics, hybridization kinetics and thermodynamics of nucleic acid self-assembly. Toward this problem, we are using our knowledge of nucleic acid 3D structure prediction, principles of hybridization and folding thermodynamics, and bioinformatics. The goal is to allow for the fully automated design of DNA and RNA nanostructures. Experimentally, we use a wide variety of techniques to characterize the structures including X-ray crystallography, electron microscopy, FRET, NMR, and gel electrophoresis. Our long-term goals are to improve the fundamental understanding of nucleic acid nano-structures, and also to make practical materials and devices.


Figure 1. Results of homology modeling of the "adenine dependent riboswitch". The structure in green is the crystal structure 1Y26.pdb and the structure colored by atom is the predicted homology model derived from 1Y27.pdb. The RMSD of the prediction is 1.24 Å (J. SantaLucia, unpublished results).



REPRESENTATIVE PUBLICATIONS

Dhimitruka, I. and SantaLucia, J., Jr. "Investigation of the Yamaguchi esterification mechanism. Synthesis of a Lux-S enzyme inhibitor using an improved esterification method", Org. Lett. 2006, 8, 47-50.

Watkins, N. E.; SantaLucia, J., Jr. "Nearest-neighbor Thermodynamics of DNA deoxyinosine pairs", Nucleic Acids Res. 2005, 33, 6258-6267.

SantaLucia, J., Jr.; Hicks, D. "The Thermodynamics of DNA Structural Motifs", Annu. Rev. Biophys. Biomol. Struct. 2004, 33, 415-440.

Jang, S.B.; Baeyens, K.; Jeong, M. S.; SantaLucia, J., Jr.; Turner, D.; Holbrook, S. R. "Structures of two RNA octamers containing tandem G-A base pairs", Acta Cryst. 60D, 2004, 60D, 829-835.

Morosyuk, S. V.; Cunningham, P. R.; SantaLucia, J., Jr. "Structure and Function of the Conserved 690 Hairpin in Escherichia coli 16 S Ribosomal RNA. II. NMR Solution Structure", J. Mol. Biol. 2001, 307, 197-211.

DEPARTMENT OF CHEMISTRY ©
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5101 Cass Ave, Detroit, MI 48202
Phone: (313) 577-7784    Fax: (313) 577-8822

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