Michael Chapman, PH.D.

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Background

Research Interests:

Macromolecular structure and function.

Virus-host interactions - structural biology of improved gene therapy vectors.

Enzymes - dynamics & mechanism.

Computational methods - modeling electron microscope images of large complexes.

X-ray crystallography, biochemical kinetics, molecular biology.

Summary of Current Research

Michael Chapman is a biophysicist who develops and applies multi-disciplinary approaches to understand viral-host interactions and enzyme mechanism / dynamics. Originally trained as a crystallographer, collaborations allow his research group to combine structural techniques - x-ray diffraction, electron microscopy (EM) & NMR spectroscopy with biochemical kinetics, molecular virology and computational modeling to understand the functional workings of large and dynamic complexes. Dr. Chapman has had a long-standing interest in developing methods to optimize structural models using diverse experimental restraints such as crystallographic maps, EM reconstructions and solid-state NMR, as well as stereochemical restraints from implicit-solvent electrostatics and idealized hydrogen-bonding, experience that will help with Aim 3. He has served in various research/administrative capacities and has mentored 30 graduate students and post-doctoral fellows, many within collaborative projects as proposed here.

Selected Publications

"Atomic modeling of cryo-electron microscopy reconstructions - Joint refinement of model and imaging parameters," Journal of Structural Biology (Vol: 182, Issue: 1, Page 10-21) - 2013

"Hyperconjugation-mediated solvent effects in phosphoanhydride bonds," Journal of Physical Chemistry A (Vol: 116, Issue: 41, Page 10209-10217) - 2012

"Crystal structures of arginine kinase in complex with ADP, nitrate, and various phosphagen analogs," Biochemical and Biophysical Research Communications (Vol: 427, Issue: 1, Page 212-217) - 2012

"Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20," Virology (Vol: 431, Issue: 1-2, Page 40-49) - 2012

"Structure of AAV-DJ, a retargeted gene therapy vector: Cryo-electron microscopy at 4.5 Ã… resolution," Structure (Vol: 20, Issue: 8, Page 1310-1320) - 2012

"Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)," Virology (Vol: 423, Issue: 1, Page 6-13) - 2012

"Crystal structures of wild-type and mutated cyclophilin B that causes hyperelastosis cutis in the American quarter horse," BMC Research Notes (Vol: 5, Issue: , Page ) - 2012

"Structure-function analysis of receptor-binding in adeno-associated virus serotype 6 (AAV-6)," Virology (Vol: 420, Issue: 1, Page 10-19) - 2011

"Rate-limiting domain and loop motions in arginine kinase," Biochemistry (Vol: 50, Issue: 19, Page 4011-4018) - 2011

"The structure of lombricine kinase: Implications for phosphagen kinase conformational changes," Journal of Biological Chemistry (Vol: 286, Issue: 11, Page 9338-9350) - 2011

"Subunit dissociation and metal binding by Escherichia coli apo-manganese superoxide dismutase," Archives of Biochemistry and Biophysics (Vol: 505, Issue: 2, Page 213-225) - 2011

"Arginine kinase: Joint crystallographic and NMR RDC analyses link substrate-associated motions to intrinsic flexibility," Journal of Molecular Biology (Vol: 405, Issue: 2, Page 479-496) - 2011

"Crystal structure of the human collagen XV trimerization domain: A potent trimerizing unit common to multiplexin collagens," Matrix Biology (Vol: 30, Issue: 1, Page 9-15) - 2011

"A pseudo-plaque method for infectious particle assay and clonal isolation of adeno-associated virus," Journal of Virological Methods (Vol: 170, Issue: 1-2, Page 9-15) - 2010

"The structure of adeno-associated virus serotype 3B (AAV-3B): Insights into receptor binding and immune evasion," Virology (Vol: 403, Issue: 1, Page 26-36) - 2010

"De-icing: Recovery of diffraction intensities in the presence of ice rings," Acta Crystallographica Section D: Biological Crystallography (Vol: 66, Issue: 6, Page 741-744) - 2010

"Intrinsic Domain and Loop Dynamics Commensurate with Catalytic Turnover in an Induced-Fit Enzyme," Structure (Vol: 17, Issue: 10, Page 1356-1367) - 2009

"Crystal Structure of Human Collagen XVIII Trimerization Domain: A Novel Collagen Trimerization Fold," Journal of Molecular Biology (Vol: 392, Issue: 3, Page 787-802) - 2009

"Adeno-associated virus-2 and its primary cellular receptor-Cryo-EM structure of a heparin complex," Virology (Vol: 385, Issue: 2, Page 434-443) - 2009

"Twinned crystals of adeno-associated virus serotype 3b prove suitable for structural studies," Acta Crystallographica Section F: Structural Biology and Crystallization Communications (Vol: 65, Issue: 2, Page 177-183) - 2009

"Anomeric effect in "high energy" phosphate bonds. Selective destabilization of the scissile bond and modulation of the exothermicity of hydrolysis," Journal of the American Chemical Society (Vol: 130, Issue: 11, Page 3349-3358) - 2008

"Crystallization and preliminary X-ray structural studies of adeno-associated virus serotype 6," Acta Crystallographica Section F: Structural Biology and Crystallization Communications (Vol: 64, Issue: 11, Page 1074-1078) - 2008

"Hydrogen bonding mediated by key orbital interactions determines hydration enthalpy differences of phosphate water clusters," Journal of Physical Chemistry A (Vol: 111, Issue: 42, Page 10804-10814) - 2007

"Normalizing Normal Mode Analysis," Structure (Vol: 15, Issue: 2, Page 135-136) - 2007

"pipath: An optimized algorithm for generating Î±-helical structures from PISEMA data," Journal of Magnetic Resonance (Vol: 183, Issue: 1, Page 87-95) - 2006