Positions

Overview

  • I am from the Pacific Northwest and received my bachelors in Biochemistry and Biophysics from Oregon State University in Corvallis, Oregon. During my time there, I did undergraduate research to examine the pre-steady state kinetic mechanism of DNA insertion catalyzed by retroviral integrase. I became intensely interested in enzyme mechanism and joined Tim Lohman’s group in the Department of Biochemistry and Molecular Biophysics at Washington University School of Medicine in St. Louis. I received my PhD in Molecular Biophysics in 2003. This was followed by postdoctoral research under the direction of Wlodek Bujalowski at the University of Texas Medical Branch (UTMB) in Galveston, Texas.

    My training experiences provided skills in the application of thermodynamic and rapid-mixing kinetic techniques to examine enzyme mechanism. In 2006 I joined the UAB Department of Chemistry as an Assistant professor. My research has been focused on understanding the molecular mechanisms of motor proteins. The work has been funded by both the NSF and NIH. I was promoted to full professor in 2015 and have graduated five PhD students in my nine year tenure during which time I was presented with the Dean’s Award for Excellence in Mentorship award.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 Examination of the nucleotide-linked assembly mechanism of E. coli ClpA 2019
    2019 Hsp104 and Potentiated Variants Can Operate as Distinct Nonprocessive Translocases 2019
    2019 A Novel Assay for RNA Polymerase i Transcription Elongation Sheds Light on the Evolutionary Divergence of Eukaryotic RNA Polymerases 2019
    2018 ATP hydrolysis inactivating Walker B mutation perturbs E. coli ClpA self-assembly energetics in the absence of nucleotide 2018
    2018 Escherichia coli DnaK Allosterically Modulates ClpB between High- and Low-Peptide Affinity States 2018
    2018 The A12.2 Subunit Is an Intrinsic Destabilizer of the RNA Polymerase I Elongation Complex 2018
    2017 Quantifying the influence of 5′-RNA modifications on RNA polymerase I activity 2017
    2017 Multisubunit RNA Polymerase Cleavage Factors Modulate the Kinetics and Energetics of Nucleotide Incorporation: An RNA Polymerase i Case Study 2017
    2017 Comparative analysis of the structure and function of AAA+ motors ClpA, ClpB, and Hsp104: Common threads and disparate functions 2017
    2017 Crystal structures of Hsp104 N-terminal domains from Saccharomyces cerevisiae and Candida albicans suggest the mechanism for the function of Hsp104 in dissolving prions 2017
    2017 Avidity for polypeptide binding by nucleotide-bound Hsp104 structures 2017
    2016 Correlating the Activity of Rhodium(I)-Phosphite-Lariat Ether Styrene Hydroformylation Catalysts with Alkali Metal Cation Binding through NMR Spectroscopic Titration Methods 2016
    2016 Examination of ClpB Quaternary Structure and Linkage to Nucleotide Binding 2016
    2015 Transient-State Kinetic Analysis of the RNA Polymerase i Nucleotide Incorporation Mechanism 2015
    2015 Examination of the dynamic assembly equilibrium for E. coli ClpB 2015
    2015 Metallathiacrown Ethers: Synthesis and Characterization of Transition-Metal Complexes Containing α,ω-Bis(phosphite)-Polythioether Ligands and an Evaluation of Their Soft Metal Binding Capabilities 2015
    2015 Escherichia coli ClpB is a non-processive polypeptide translocase 2015
    2015 Analysis of Linked Equilibria 2015
    2015 Examination of polypeptide substrate specificity for Escherichia coli ClpB 2015
    2014 Characterization of calmodulin-fas death domain interaction: An integrated experimental and computational study 2014
    2014 ATPγS competes with ATP for binding at Domain 1 but not Domain 2 during ClpA catalyzed polypeptide translocation 2014
    2013 E. coli ClpA catalyzed polypeptide translocation is allosterically controlled by the protease ClpP 2013
    2013 Examination of the polypeptide substrate specificity for escherichia coli ClpA 2013
    2012 Dynamic light scattering to study allosteric regulation 2012
    2011 Generally applicable NMR titration methods for the determination of equilibrium constants for coordination complexes: Syntheses and characterizations of metallacrown ethers with α,ω-bis(phosphite)- Polyether ligands and determination of equilibrium binding constants to li+ 2011
    2011 Activity of E. coli ClpA bound by nucleoside diphosphates and triphosphates 2011
    2011 An Examination of the Kinetic Mechanism of the ATP-Dependent Protease ClpAP 2011
    2011 Structural and Functional Studies of the E. Coli ClpA Molecular Motor 2011
    2011 Application of the sequential n-step kinetic mechanism to polypeptide translocases 2011
    2010 Effect of temperature on the self-assembly of the Escherichia coli ClpA molecular chaperone 2010
    2010 Implementing and evaluating a chemistry course in chemical ethics and civic responsibility 2010
    2010 Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors 2010
    2010 Molecular mechanism of polypeptide translocation catalyzed by the Escherichia coli ClpA Protein Translocase 2010
    2009 The Escherichia coli ClpA molecular chaperone self-assembles into tetramers 2009
    2008 Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A 2008
    2006 Allosteric interactions between the nucleotide-binding sites and the ssDNA-binding site in the PriA helicase-ssDNA complex. 3 2006
    2006 Kinetic mechanisms of the nucleotide cofactor binding to the strong and weak nucleotide-binding site of the Escherichia coli PriA helicase. 2 2006
    2006 The Escherichia coli PriA helicase has two nucleotide-binding sites differing dramatically in their affinities for nucleotide cofactors. 1. Intrinsic affinities, cooperativities, and base specificity of nucleotide cofactor binding 2006
    2006 DNA polymerase X from African swine fever virus: Quantitative analysis of the enzyme-ssDNA interactions and the functional structure of the complex 2006
    2005 Energetics of DNA end binding by E. coli RecBC and RecBCD helicases indicate loop formation in the 3′-single-stranded DNA tail 2005
    2005 Binding of six nucleotide cofactors to the hexameric helicase RepA protein of plasmid RSF1010. 1. Direct evidence of cooperative interactions between the nucleotide-binding sites of a hexameric helicase 2005
    2005 Binding of six nucleotide cofactors to the hexameric helicase RepA protein of plasmid RSF1010. 2. Base specificity, nucleotide structure, magnesium, and salt effect on the cooperative binding of the cofactors 2005
    2005 Interactions of nucleotide cofactors with the Escherichia coli replicative helicase PriA 2005
    2004 Effects of temperature and ATP on the kinetic mechanism and kinetic step-size for E. coli RecBCD helicase-catalyzed DNA unwinding 2004
    2004 Fluorescence stopped-flow studies of single turnover kinetics of E. coli RecBCD helicase-catalyzed DNA unwinding 2004
    2003 DNA helicases, motors that move along nucleic acids: Lessons from the SF1 helicase superfamily 2003
    2003 General methods for analysis of sequential "n-step" kinetic mechanisms: Application to single turnover kinetics of helicase-catalyzed DNA unwinding 2003
    2003 Kinetic mechanism for E. coli RecBCD-catalyzed DNA unwinding studied by fluorescence stopped-flow methods 2003
    2002 DNA unwinding step-size of E. coli RecBCD helicase determined from single turnover chemical quenched-flow kinetic studies 2002
    2000 DNA unwinding step-size of E-coli recBCD helicase. 2000

    Research Overview

  • The fundamental question that my group seeks to address is, how does a motor protein couple the energy from ATP binding and hydrolysis to perform mechanical work? To address this question we use chemical quenched-flow and fluorescence stopped-flow assays. Both techniques allow us to rapidly mix two reagents within 2 ms and observe a reaction on the millisecond time scale, which, in most cases, is the appropriate temporal resolution for enzyme catalysis.

    To both design and interpret the rapid mixing kinetic experiments, one requires knowledge of the energetics of the binding and assembly reactions that occur. To address these questions, we use an array of thermodynamic, hydrodynamic, and spectroscopic approaches. These include analytical ultracentrifugation, dynamic and static light scattering, fluorescence titrations, and isothermal titration calorimetry (ITC), among others.

    Just like physics seeks to describe phenomena with mathematics, biophysics seeks to describe molecular level events with mathematics. Thus, a major component of our work is using mathematics to quantitatively describe the observed physical phenomena. This is accomplished by using tools like Mathematica and Matlab to solve complex systems of both coupled differential and coupled algebraic equations. The derived solutions can then be used to model and describe the experimental results. This can often require coding in Matlab, C++, or Fortran.

    In total, the research truly lies at the interface between Chemistry, Biology, Physics, and Mathematics. There is a place in my research group for members from each discipline.

    Keywords - Physical Chemistry, Biophysical Chemistry, Thermodynamics of Protein-protein and Protein-ligand Interactions, Pre-steady State Kinetics, Enzyme Mechanism, and Motor Proteins
  • Teaching Activities

  • CH325 - Physical Chemistry I (Fall Term 2019) 2019
  • CH325L - Physical Chemistry I Lab (Fall Term 2019) 2019
  • CH325L - Physical Chemistry I Lab (Fall Term 2019) 2019
  • CH325L - Physical Chemistry I Lab (Fall Term 2019) 2019
  • CH729 - Spec Topics in Physical Chem (Fall Term 2019) 2019
  • CH791 - Seminar (Fall Term 2019) 2019
  • CH792 - Seminar Presentation (Fall Term 2019) 2019
  • CH798 - Non-Dissertation Research (Fall Term 2019) 2019
  • CH799 - Dissertation Research (Fall Term 2019) 2019
  • CH798 - Non-Dissertation Research (Summer Term 2019) 2019
  • CH799 - Dissertation Research (Summer Term 2019) 2019
  • CH463 - Biochemistry Laboratory (Summer Term 2019) 2019
  • CH763 - Biochemistry Laboratory (Summer Term 2019) 2019
  • CH791 - Seminar (Spring Term 2019) 2019
  • CH792 - Seminar Presentation (Spring Term 2019) 2019
  • CH798 - Non-Dissertation Research (Spring Term 2019) 2019
  • CH799 - Dissertation Research (Spring Term 2019) 2019
  • CH325 - Physical Chemistry I (Fall Term 2018) 2018
  • CH325L - Physical Chemistry I Lab (Fall Term 2018) 2018
  • CH325L - Physical Chemistry I Lab (Fall Term 2018) 2018
  • CH325L - Physical Chemistry I Lab (Fall Term 2018) 2018
  • CH729 - Spec Topics in Physical Chem (Fall Term 2018) 2018
  • CH791 - Seminar (Fall Term 2018) 2018
  • CH792 - Seminar Presentation (Fall Term 2018) 2018
  • CH798 - Non-Dissertation Research (Fall Term 2018) 2018
  • CH799 - Dissertation Research (Fall Term 2018) 2018
  • CH798 - Non-Dissertation Research (Summer Term 2018) 2018
  • CH799 - Dissertation Research (Summer Term 2018) 2018
  • CH798 - Non-Dissertation Research (Spring Term 2018) 2018
  • CH799 - Dissertation Research (Spring Term 2018) 2018
  • CH325 - Physical Chemistry I (Fall Term 2017) 2017
  • CH325L - Physical Chemistry I Lab (Fall Term 2017) 2017
  • CH325L - Physical Chemistry I Lab (Fall Term 2017) 2017
  • CH325L - Physical Chemistry I Lab (Fall Term 2017) 2017
  • CH798 - Non-Dissertation Research (Fall Term 2017) 2017
  • CH799 - Dissertation Research (Fall Term 2017) 2017
  • CH798 - Non-Dissertation Research (Summer Term 2017) 2017
  • CH799 - Dissertation Research (Summer Term 2017) 2017
  • CH463 - Biochemistry Laboratory (Summer Term 2017) 2017
  • CH763 - Biochemistry Laboratory (Summer Term 2017) 2017
  • CH791 - Seminar (Spring Term 2017) 2017
  • CH792 - Seminar Presentation (Spring Term 2017) 2017
  • CH798 - Non-Dissertation Research (Spring Term 2017) 2017
  • CH799 - Dissertation Research (Spring Term 2017) 2017
  • CH325 - Physical Chemistry I (Fall Term 2016) 2016
  • CH325L - Physical Chemistry I Lab (Fall Term 2016) 2016
  • CH325L - Physical Chemistry I Lab (Fall Term 2016) 2016
  • CH325L - Physical Chemistry I Lab (Fall Term 2016) 2016
  • CH525 - Physical Chem I for Grad Study (Fall Term 2016) 2016
  • CH700 - Foundations of Phys/Analy Chem (Fall Term 2016) 2016
  • CH790 - Intro to Graduate Research (Fall Term 2016) 2016
  • CH791 - Seminar (Fall Term 2016) 2016
  • CH792 - Seminar Presentation (Fall Term 2016) 2016
  • CH798 - Non-Dissertation Research (Fall Term 2016) 2016
  • CH799 - Dissertation Research (Fall Term 2016) 2016
  • CH798 - Non-Dissertation Research (Summer Term 2016) 2016
  • CH799 - Dissertation Research (Summer Term 2016) 2016
  • CH463 - Biochemistry Laboratory (Summer Term 2016) 2016
  • CH763 - Biochemistry Laboratory (Summer Term 2016) 2016
  • CH791 - Seminar (Spring Term 2016) 2016
  • CH792 - Seminar Presentation (Spring Term 2016) 2016
  • CH798 - Non-Dissertation Research (Spring Term 2016) 2016
  • CH799 - Dissertation Research (Spring Term 2016) 2016
  • CH325 - Physical Chemistry I (Fall Term 2015) 2015
  • CH325L - Physical Chemistry I Lab (Fall Term 2015) 2015
  • CH325L - Physical Chemistry I Lab (Fall Term 2015) 2015
  • CH325L - Physical Chemistry I Lab (Fall Term 2015) 2015
  • CH429 - Spec Topics in Physical Chem (Fall Term 2015) 2015
  • CH700 - Foundations of Phys/Analy Chem (Fall Term 2015) 2015
  • CH463 - Biochemistry Laboratory (Summer Term 2015) 2015
  • CH461 - Advanced Biochemistry I (Spring Term 2015) 2015
  • CH464 - Physical Biochemistry Lab (Spring Term 2015) 2015
  • CH561 - Advanced Biochemistry I (Spring Term 2015) 2015
  • CH761 - Biochemistry II (Spring Term 2015) 2015
  • CH325 - Physical Chemistry I (Fall Term 2014) 2014
  • CH325L - Physical Chemistry I Lab (Fall Term 2014) 2014
  • CH325L - Physical Chemistry I Lab (Fall Term 2014) 2014
  • CH325L - Physical Chemistry I Lab (Fall Term 2014) 2014
  • CH525 - Physical Chem I for Grad Study (Fall Term 2014) 2014
  • CH700 - Foundations of Phys/Analy Chem (Fall Term 2014) 2014
  • CH463 - Biochemistry Laboratory (Summer Term 2014) 2014
  • CH763 - Biochemistry Laboratory (Summer Term 2014) 2014
  • CH461 - Advanced Biochemistry I (Spring Term 2014) 2014
  • CH464 - Physical Biochemistry Lab (Spring Term 2014) 2014
  • CH561 - Advanced Biochemistry I (Spring Term 2014) 2014
  • CH761 - Biochemistry II (Spring Term 2014) 2014
  • CH325 - Physical Chemistry I (Fall Term 2013) 2013
  • CH325L - Physical Chemistry I Lab (Fall Term 2013) 2013
  • CH325L - Physical Chemistry I Lab (Fall Term 2013) 2013
  • CH325L - Physical Chemistry I Lab (Fall Term 2013) 2013
  • CH525 - Physical Chem I for Grad Study (Fall Term 2013) 2013
  • CH700 - Foundations of Phys/Analy Chem (Fall Term 2013) 2013
  • CH463 - Biochemistry Laboratory (Summer Term 2013) 2013
  • CH461 - Advanced Biochemistry I (Spring Term 2013) 2013
  • CH464 - Physical Biochemistry Lab (Spring Term 2013) 2013
  • CH561 - Biochemistry I (Spring Term 2013) 2013
  • CH761 - Biochemistry II (Spring Term 2013) 2013
  • CH325 - Physical Chemistry I (Fall Term 2012) 2012
  • CH325L - Physical Chemistry I Lab (Fall Term 2012) 2012
  • CH325L - Physical Chemistry I Lab (Fall Term 2012) 2012
  • CH325L - Physical Chemistry I Lab (Fall Term 2012) 2012
  • CH525 - Physical Chem I for Grad Study (Fall Term 2012) 2012
  • CH700 - Foundations of Phys/Analy Chem (Fall Term 2012) 2012
  • CH463 - Biochemistry Laboratory (Summer Term 2012) 2012
  • CH763 - Biochemistry Laboratory (Summer Term 2012) 2012
  • CH461 - Advanced Biochemistry I (Spring Term 2012) 2012
  • CH464 - Physical Biochemistry Lab (Spring Term 2012) 2012
  • CH761 - Biochemistry II (Spring Term 2012) 2012
  • CH764 - Biophysical Chemistry (Spring Term 2012) 2012
  • CH325 - Physical Chemistry I (Fall Term 2011) 2011
  • CH325L - Physical Chemistry I Lab (Fall Term 2011) 2011
  • CH325L - Physical Chemistry I Lab (Fall Term 2011) 2011
  • CH325L - Physical Chemistry I Lab (Fall Term 2011) 2011
  • CH525 - Physical Chem I for Grad Study (Fall Term 2011) 2011
  • CH700 - Foundations of Phys/Analy Chem (Fall Term 2011) 2011
  • CH463 - Biochemistry Laboratory (Summer Term 2011) 2011
  • CH763 - Biochemistry Laboratory (Summer Term 2011) 2011
  • CH461 - Advanced Biochemistry I (Spring Term 2011) 2011
  • CH493 - Chemistry in Culture & Ethics (Spring Term 2011) 2011
  • CH495 - Ethics in Chemical Research (Spring Term 2011) 2011
  • CH761 - Biochemistry II (Spring Term 2011) 2011
  • CH325 - Thermodynamics/Chem Kinetics (Fall Term 2010) 2010
  • CH325L - Thermodynam/Chem Kinetics Lab (Fall Term 2010) 2010
  • CH325L - Thermodynam/Chem Kinetics Lab (Fall Term 2010) 2010
  • CH325L - Thermodynam/Chem Kinetics Lab (Fall Term 2010) 2010
  • CH525 - Physical Chem I for Grad Study (Fall Term 2010) 2010
  • CH700 - Foundtions of Phys/Analy Chem (Fall Term 2010) 2010
  • CH463 - Biochemistry Laboratory (Summer Term 2010) 2010
  • CH763 - Biochemistry Laboratory (Summer Term 2010) 2010
  • CH461 - Advanced Biochemistry I (Spring Term 2010) 2010
  • CH661 - Biochemistry II (Spring Term 2010) 2010
  • CH761 - Biochemistry II (Spring Term 2010) 2010
  • CH600 - Found of Phys/Analy Chem (Fall Term 2009) 2009
  • CH700 - Foundtions of Phys/Analy Chem (Fall Term 2009) 2009
  • CH463 - Biochemistry Laboratory (Summer Term 2009) 2009
  • CH563 - Biochemistry Laboratory (Summer Term 2009) 2009
  • CH105 - Introductory Chemistry I (Spring Term 2009) 2009
  • CH320 - Chemistry in Culture & Ethics (Spring Term 2009) 2009
  • CH105 - Introductory Chemistry I (Fall Term 2008) 2008
  • CH463 - Biochemistry Laboratory (Summer Term 2008) 2008
  • CH563 - Biochemistry Laboratory (Summer Term 2008) 2008
  • CH105 - Introductory Chemistry I (Spring Term 2008) 2008
  • CH100 - Chemical Problem Solving (Fall Term 2007) 2007
  • CH700 - Foundtions of Phys/Analy Chem (Fall Term 2007) 2007
  • Education And Training

  • Johns Hopkins University Biophysics, Other 2018
  • University of Texas Medical Branch at Galveston Biochemistry and Molecular Biology, Postdoctoral Research 2006
  • Full Name

  • Aaron Lucius