The following outline presents brief descriptions of several projects in my group.  The specific focus of these projects is fluid and other projects are possible, so please stop in and see me for more details.

Predicting fluorescent probe motions using molecular dynamics calculations.  Fluorescent probes are used in many biophysical studies to report about the properties of proteins and nucleic acids.  In many studies, the relative orientations of the probes are key.  We will use molecular dynamics (MD) simulation methods to calculate probe motions, giving us a detailed, atomic-scale picture of the fluorescent probes and their proteins.  Initial work will involve lysozyme, a commonly used enzyme to which a dye can be bound non-covalently, or covalently, providing two very different tests for our simulation methods.

The dynamics of structural change in phospholamban.  Phospholamban (PLB) is a regulatory protein that helps maintain normal cardiac function.  PLB transitions between monomeric and oligomeric (presumed to be pentameric) states.  We will first seek to measure the size of the oligomeric state of PLB using time-resolved fluorescence methods.  In short, PLB monomers are labeled with one of two fluorescent probes and then mixed to make oligomers.  The fluorescence decays of the two dyes are characteristic of the oligomeric size.  The second stage of the work will measure the dynamics of the transition from monomer to oligomer.  This information is crucial to understanding the details of how cardiac function is regulated by PLB.  All work with PLB will be conducted in collaboration with the Dave Thomas laboratory at the University of Minnesota.

Calculating the free energy of binding in phospholamban.  Phospholamban (see above) holds promise as a pharmaceutical target to improve cardiac function.  Any serious pharmaceutical work on PLB must begin with a detailed understanding of how PLB monomers bind together to form an oligomer and how monomers bind to their target, the cardiac calcium pump.  We will utilize a new computational method, called MM-PBSA, to estimate the binding free energies mentioned above.  One benefit of this method is the ease with which we can analyze mutational variations.  This allows careful comparison to a wide range of experimental studies -- not always possible with calculations.  In total, these studies will reveal, with atomic detail, how PLB achieves its biological function. 

Development of a mixed MD-QM method for comparing simulation with experiment.  Many spectroscopic studies on biological systems have revealed a need to understand the connection between biologically important pigments and the proteins that bind them.  For instance, all photosynthetic systems rely on proteins that bind chlorophyll (and other pigments) tightly enough to be able to modify its properties, but loosely enough to minimize the loss of solar energy.  This careful balance must be dynamically tuned by the organism to maintain optimal function.  To understand how nature has constructed these protein-pigment systems to achieve efficient and versatile function, we must understand how protein motions are connected to the spectroscopic properties of the pigments.  We will use a combination of molecular dynamics (MD) and quantum mechanical (QM) calculations to simulate the proteins motions (MD) and their effects on the pigments (QM).  This work will provide a close link between calculations and spectroscopic experiments that does not currently exist.  In the longer term, we hope to provide the kind of detailed understanding of photosynthetic function that will lead to new materials for the efficient use of solar energy.