Expertise:
- Skeletal and cardiac muscle research. Hypertrophic cardiomyopathy (HCM). Study of the actin-myosin interaction, the effect of small compounds on the powerstroke, and of the structural dynamics of myosin essential and regulatory light chains during muscle contraction. Electron paramagnetic spectroscopy (EPR), Fluorescence resonance energy transfer (FRET), Fluorescence quenching, transient kinetics of myosin ATPase pathway, Muscle fiber mechanics, and design and develop FRET biosensors for small molecule discovery.
Research statement
My research goal is to study the molecular mechanism of muscle contraction, with an emphasis on hypertrophic cardiomyopathy (HCM) disease. I am using multidisciplinary approaches such as biochemistry (steady state and transient kinetics), molecular biology (site-directed mutagenesis of muscle proteins to introduce probes), muscle mechanics, and biophysics (spectroscopy) to solve fundamental problems in the mechanism of muscle contractility. I use fluorescence resonance energy transfer (FRET), and electron paramagnetic resonance (EPR) spectroscopies to study the myosin-actin interaction and the lever arm rotation in solution and in muscle fibers. I am also developing fluorescent myosin biosensors for high-throughput screening assays for small compounds. Collaborators: Dr. David D. Thomas, Dr. Piyali Guhathakurta
Recent/relevant publications
J. A., Rohde, O. Roopnarine, D. D. Thomas, J. M. Muretta. 2018. Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin. Proc Natl Acad Sci U S A.115(32):E7486-E7494. PMID: 30018063
P. Guhathakurta, E. Prochniewicz, O. Roopnarine, J. A. Rohde, and D. D. Thomas. 2017. A Cardiomyopathy Mutation in the Myosin Essential Light Chain Alters the Structural Interaction with Actin. Biophys. J.113:91-100. PMID: 28700929
O. Roopnarine. 2003. Mechanical defects of muscle fibers with myosin light chain mutants that cause cardiomyopathy. Biophys. J., 84:2440-2449. PMID: 12668451
O. Roopnarine. 2002. Familial Hypertrophic Cardiomyopathic myosin mutations that affect the actin-myosin interaction. In Molecular Interactions of Actin. Actin-Myosin Interaction and Actin-Based Regulation. Springer-Verlag Berlin Heidelberg, Germany. Results Probl. Cell. Differ. 36:75-86. PMID: 11892286
D. D. Thomas, E. Prochniewicz and O. Roopnarine. 2002. Changes in Actin and Myosin Structural Dynamics Due to Their Weak and Strong Interactions. In Molecular Interactions of Actin. Actin-Myosin Interaction and Actin-Based Regulation. Springer-Verlag Berlin Heidelberg, Germany. Results Probl. Cell. Differ. 36:7-19. PMID: 11892285
D. D. Thomas and O. Roopnarine. 2002. An overview of the actomyosin interaction. In Molecular Interactions of Actin. Actin-Myosin Interaction and Actin-Based Regulation. Springer-Verlag Berlin Heidelberg, Germany. Results Probl. Cell. Differ. 36:1-5.
O. Roopnarine and L.A. Leinwand. 1998. Functional analysis of myosin mutations that cause familial hypertrophic cardiomyopathy. Biophys. J., 75:3023-3030. PMID: 9826622
O. Roopnarine, A.G. Szent-Györgyi, and D.D. Thomas. 1998. Microsecond rotational dynamics of spin-labeled myosin regulatory light chain induced by relaxation and contraction of scallop muscle. Biochemistry, 37:14428-14436. PMID: 9772169
O. Roopnarine and D.D. Thomas. 1996. Orientational dynamics of intermediate nucleotide states of indane dione spin-labeled myosin heads in skeletal muscle fibers. Biophys. J., 70:2795-2806. PMID: 8744317
O. Roopnarine and D.D. Thomas. 1995. Orientational dynamics of indane-dione spin-labeled myosin heads in relaxed and contracting skeletal muscle fibers. Biophys. J., 68:1461-1471. PMID: 7787032
O. Roopnarine, A.G. Szent-Györgyi, and D.D. Thomas. 1995. Saturation transfer electron paramagnetic resonance of spin-labeled myosin regulatory light chains in contracting muscle fibers. Biophys. J. 68:337s
Thomas, D.D., R. Ramachandran, O. Roopnarine, D.W. Hayden and E.M. Ostap. 1995. The mechanism of force generation in myosin, a disorder-to-order transition, coupled to internal structural changes. Biophys. J., 68:135s-141s. PMID: 7787056
O. Roopnarine and D.D. Thomas. 1994. A spin label that binds to myosin heads in muscle fibers with its principal axis parallel to the fiber axis. Biophys. J., 67:1634-1645. PMID: 7819495
O. Roopnarine, K. Hideg, and D.D. Thomas. 1993. Saturation Transfer EPR of an Indane-Dione Spin-Label: Calibration with Hemoglobin and Application to Myosin Rotational Dynamics. Biophys. J., 64:1896-1906. PMID: 8396449
P. James, A.K. Alrich, O. Roopnarine and J. Parker. 1989. Context specific misreading of phenylalanine codons. Molecular General Genetics 218:397-401. PMID: 2685541