Professor and Department Head
My research interests are focused on developing and applying computational methods to study reactions of biochemical interest. The reactions of interest include the collapse of a nascent polypeptide chain to its compact native structure, the association of two proteins, for instance different subunits in a multisubunit complex or redox partners in an electron transfer complex, the association of nucleic acids with nucleic acid binding proteins, or the binding of small ligands to either DNA or enzymes.
In order to study these reactions, I utilize a variety of computational techniques including ab initio and semi-empirical quantum mechanical calculations, classical molecular mechanics and dynamics calculations, conformer searching, and free energy calculations, as well as sequence alignment and structure prediction techniques.
Currently, I am particularly interested in enzymes which play a critical role in detoxification of potentially hazardous compounds. These enzymes include cyctochromes P450 and glutathione S-transferases which metabolize a wide variety of aliphatc and aromatic compound, phosphotriesterases which degrade organophosphate neurotoxins, and haloalkane dehalogenase and haloacid dehalogenase both of which metabolize simple halogenated aliphatics.
G. D. Szklarz, S. E. Graham, and M. D. Paulsen, "Molecular Modeling of Mammalian Cytochromes P450: Application to the study of enzyme function" (submitted).
Mark D. Paulsen and B. P. Hay "Conformational Analysis of Crown Ethers 3: Alkali Metal and Alkaline Earth Complexes of 15-Crown-5" Theochem., 1998 429, 49-59.
Mark D. Paulsen, J. R. Rustad, and B. P. Hay "Conformational Analysis of Crown Ethers 2: 15 Crown-5" Theochem., 1997, 397, 1-12.
Mark D. Paulsen "Using Free Energy Calculations to Optimize Force Field Parameters" in Proceedings of the 34th Hanford Symposium on Health and the Environment, (R. Ornstein, ed.) Battelle Press, Columbus, Ohio, 1997 p. 183-192.
Mark D. Paulsen and Tjerk P. Straatsma "Chlorinated Ethanes in Aqueous Solution: Parameterization based on Thermodynamics of Hydration" Chem. Phys. Lett., 1996, 259, 142-145.
Mark D. Paulsen and Rick L. Ornstein "Binding Free Energy Calculations for P450cam-Substrate Complexes " Prot. Engineering 1996, 9, 567-571.
Mark D. Paulsen, John, I. Manchester, and Rick. L. Ornstein "Using Molecular Modeling and Molecular Dynamics Simulation to Predict P450 Oxidation Products" Meth. in Enzymol. 1996, 272, 347
Paul J. Loida, Stephen G. Sligar, Mark D. Paulsen, Gregory E. Arnold, and Rick L. Ornstein "Stereoselective Hydroxylation of Norcamphor by Cytochrome P450cam: Experimental Verification of Molecular Dynamics Simulations" J. Biol. Chem. 1995, 270, 5326-5330.
I earned my BS in Chemistry from the University of Nebraska-Lincoln and my PhD from the University of Wisconsin-Madison.
Prior to coming to Northern Michigan University, I work in the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory which is part of the Department of Energy laboratory system.
I also taught at Washington State University in the Department of Biochemistry and Biophysics.