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Mike Yonkunas

Contact Information:
Department of Chemistry Carnegie Mellon University 508 Mellon Institute
Email: myonkuna@andrew.cmu.edu

Education:
1996 - 2000 - B.S. Physics Millersville University, Millersville, PA
2005 - - PhD Molecular Biophysics Carnegie Mellon University

Professional Memberships
1999–2001 Member, American Physical Society
2003-present Member, Biophysical Society

Research:
Investigating the role of electrostatic interactions in Glutamate receptor mechanism by multi-scale theoretical modeling. Elevated levels of glutamate during cerebral ischemia play a major role in �excitotoxicity� of glutamate receptors (GluRs) leading to neuron death and devastating effects on the central nervous system. Studies show that antagonists of the AMPA GluR subtype have a neuroprotective effect on a variety of ischemic models. Functional diversity of GluR in the brain is revealed in clinical trials showing antagonists produce such side effects as developmental dysfunction and psychosis. Clearly understanding the mechanism by which GluRs function is critical for rational drug design which may provide neuroprotection over antagonists of the receptor. More importantly exploring subtle differences in receptor subtypes provide a means of drug specificity, eliminating potential side effects. Structural and theoretical (Speranskiy et al. Biochem.. 2005 Aug 30;44(34):11508) studies of AMPA receptors indicate that electrostatic interactions play an important role in both ligand attraction to the ligand binding S1-S2 extracellular domain, and interactions at the S1-S2 domain interface. Modeling the conformational change in S1-S2 that occurs upon ligand binding indicate the ligand bound conformation may be stabilized by hydrogen bonding and long-range electrostatic attraction. These results contribute to the current working hypothesis that electrostatic interactions play an important role in the glutamate receptor function. A multiple-methodology is being used to study GluR function using long molecular dynamics trajectories. Also being conducted is a rigorous Investigation of the interactions between the extracellular domain dimer and surface of the lipid bilayer through Monte Carlo simulations and electrostatic Poisson-Boltzmann theory.

PhD Advisor:
Dr. Maria Kurnikova Research Group

Research Advisor:
I. Rob Coalson (in collaboration with Sunil Saxena)
Department of Chemistry University of Pittsburgh
Exploring the Unfolded States of Polyalanine through Molecular Dynamics Simulations Using EPR Restraints.

II. Maria Kurnikova
Department of Chemistry Carnegie Mellon University
The Biochemically Identified Binding Site of a Set of Ligand Gated Ion Channels Investigated by Molecular Docking.

III. Pei Tang
Department of Structural Biology and Molecular Biophysics University of Pittsburgh Medical School
Exploring Functional Similarities and Differences between two Ligand Gated Ion Channel subtypes through Anesthetic Docking and Molecular Dynamics Simulations.

Publications:
Selected peer reviewed publications (in chronological order).
1. Yonkunas MJ, Xu Y, Tang P., Anesthetic Interaction with Ketosteroid Isomerase: Insights from Molecular Dynamics Simulations. Biophysical Journal (2004) Oct;89(4):2350-2356.

2. Li L, Geng X, Yonkunas M, Su A, Densmore E, Tang P, Drain P., Ligand-dependent linkage of the ATP site to inhibition gate closure in the KATP channel. Journal of General Physiology (2005) Sep;126(3):285-299.

3. Jun S, Becker JS, Yonkunas M, Coalson R, Saxena S., Unfolding of alanine-based peptides using electron spin resonance distance measurements. Biochemistry (2006) Sep 26;45(38):11666-11673..

Selected abstracts (in chronological order).
(Selected from a total of 7 abstracts)

1. Michael J. Yonkunas, Dejian Ma, Zhanwu Liu, Ling Li, Yan Xu, Pei Tang., (2004) Allosteric Low-Affinity Drug Action on Ketosteroid Isomerase. The 48th Annual Biophysical Society Meeting, Baltimore, MD.

2. Yan Xu, Michael J. Yonkunas, Dejian Ma, Zhanwu Liu, Ling Li, Pei Tang., (2004) Protein Dynamics as a Common Molecular Mechanism of General Anesthetic Action. The 51st AUA Annual Meeting, Sacramento, CA.

3. Michael J. Yonkunas, Yan Xu, Pei Tang., (2005) Anesthetic Interaction with Calmodulin. The 49th Annual Biophysical Society Meeting, Long Beach, CA.

4. Michael J. Yonkunas, Zhenyu Liu, Kirill Speranskiy, Mike Cascio, Maria Kurnikova., (2007) Investigating the Ligand Binding Site of Acetylcholine Binding Protein and the Glycine Receptor. The 51st Annual Biophysical Society Meeting, Baltimore, MD.