Jane Aldrich, Graduate Student Researcher
John Anderson, Staff
John P. Clark, Graduate Student Researcher
David G. Garrett, Lockheed Martin, St. Paul, Minnesota
Stephanie Kerimo, Undergraduate Student Researcher
Quang Le, Department of Family Practice, Hennepinn County Hospital, Minneapolis, Minnesota
Kenneth E. Lind, Graduate Student Researcher
Nonzpa Lyfoung, Undergraduate Student Researcher
Ian Mcfadyen, Research Associate
Thomas G. Metzger, Research Associate
Venkatraman Mohan, ISIS Pharmaceuticals, Carlsbad, California
M. Germana Paterlini, Adjunct Faculty Collaborator
Gennady Poda, Supercomputing Institute Research Scholar
Mahadevan Seetharaman, Graduate Student Researcher
Govindan Subramanian, Research Associate
Divi Venkateswarlu, Research Associate
Haiqing Wang, Graduate Student Researcher
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"Structural Properties of DNA:RNA Duplexes Containing 2'-O-methyl and 2'-S-methyl Substitutions: A Molecular Dynamics Investigation," D. Venkateswarlu, K.E. Lind, V. Mohan, M. Manoharan, and D.M. Ferguson, Nucleic Acids Research, 27, p. 2189 (1999). |
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"Effects of C2'-Substitution on Arabinonucleic Acid Structure And Conformation," D. Venkateswarlu and D.M. Ferguson, Journal of the American Chemical Society, 121, p. 5609 (1999). |
The structure, function, and dynamics of macromolecules and macromolecular interactions are studied using a variety of computational techniques including molecular graphics, empirical force fields, ab initio calculations, molecular docking, and molecular dynamics simulations. The primary emphasis of this work is on the development and application of structural models of G protein-coupled receptors (GPCRs) to ligand design. In particular, interest is in developing highly selective opioid ligands with modified pharmacological properties.
A second area of emphasis is placed on studying the structure, dynamics, and thermodynamic stability of modified nucleic acid complexes for use in antisense drug development. Molecular dynamics calculations are performed on several nucleic acid systems in an effort to investigate the effect of single base pair mismatches. Experimental data has shown specific mutations may allow activity to be "turned on" or "off," which may suggest a mechanism for gene regulation. Molecular dynamics simulations of the wild-type and mutant will be conducted to evaluate potential structure-function relationships. Calculations and analyses will be performed using the amber suite of programs available at the Supercomputing Institute/Medicinal Chemistry Visualization-Workstation Laboratory. Initial starting structures will be generated using crystallographic data available through the Brookhaven Protein Databank. The results are then used to develop strategies to regulate gene expression and transcription/translation.
Both projects require significant force field parameterization, ab initio model calculations, and long time scale molecular dynamics simulations as well as graphics visualizations. The long term goal of this work is to model molecular recognition processes reliably and confidently for use in drug design and development.
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URL: http://www.msi.umn.edu/about/publications/annualreport/ar2000/depts/Pharmacy/MedChem/ferguson.html |
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