Michael Rynkiewicz, Ph.D.
Instructor of Pharmacology, Physiology & Biophysics
I am a protein crystallographer with extensive experience in computational structural analysis. My work over the years has encompassed a broad range of techniques, including protein crystallography, kinetic assays, organic synthesis, NMR and ultraviolet spectroscopy, small molecule structure-based drug design, epitope mapping of antibodies, and molecular dynamics calculations.
Current Research
Mechanism of tropomyosin activation probed by energy landscape analysis. Muscle contraction is regulated in part by tropomyosin. The tropomysosin molecules wrap around actin thin filaments in the sarcomere, and the position of the tropomyosin chain regulates the binding of myosin to the thin filament. The regulatory transitions of tropomyosin have been mapped out by a variety of techniques including negative stain and cryo electron microscopy and computational studies. However, the electron microscopy structures only provide a static picture of tropomyosin during regulation, any dynamic information is lost. Many cardiomyopathies derive their deleterious cardiovascular effects from mutations of tropomyosin. Presumably, these mutations alter the regulatory transitions of tropomyosin in subtle ways that lead to aberrant cardiac function. By studying the energy of tropomyosin at discreet locations on the actin filament for mutant and wild-type tropomyosins, we hope to learn the root causes of these cardiomyopathies and propose mechanisms by which they develop.