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Johns Hopkins University logoProgram in Molecular Biophysics
Margaret JohnsonJohnson Lab



Assistant Professor
Thomas C. Jenkins Department of Biophysics
Krieger School of Arts & Sciences


B.S. 2004, Columbia University
Ph.D. 2009, University of California, Berkeley


margaret.johnson@jhu.edu

201 Jenkins Hall
3400 N. Charles Street
Baltimore, MD 21218

Office: 410-516-2376
Lab:

 

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The dynamic assembly of multiple proteins into large functional complexes at specific times and places in the cell is a crucial step in cellular functions ranging from endocytic trafficking of membrane cargo to DNA transcription and actin polymerization. The protein-protein interactions that control such cellular processes are diverse and dynamic, forming a network of connections that can nucleate and stabilize extended protein complexes. Despite much experimental studies on the details of the proteins involved, their binding reactions, and the structure of completed assemblies, the evolution and mechanisms of many multi-protein assembly processes remains unresolved. Using computer simulation and theoretical models, we are able to build detailed models of the dynamics of protein assembly and provide predictions of how the timing of these events in the cell are controlled by the concentrations of proteins in the cytosol and membrane. Our approach combines systems level research on protein networks that investigates both general, governing principles of protein dynamics, and applications to several specific protein assembly systems.

A major research focus is on developing accurate physical models to describe the spatio-temporal dynamics of populations of proteins in the cell and developing computational tools to analyze these multi-scale simulations. Building accurate models of biological systems requires accounting for the network of protein-interface interactions. We are also using coarse-grained models to characterize more generally how the topology of protein interaction networks affects the specificity and dynamics of protein binding. These network based studies complement the more detailed computer simulations by establishing how the connectivity of a protein within a larger network affects its local dynamic.

Clathrin-mediated endocytosis is one central pathway in the cell that relies on multi-protein assembly of a clathrin protein coat at the plasma membrane to successfully internalize extracellular cargo into the cell. Endocytosis is essential for life, not only because it transports nutrients for cell growth, but also because it regulates signal communication between cells. Characterizing the steps leading up to cargo internalization is critical for understanding how endocytic function is controlled in healthy and diseased cells as, for example, viral infections can result when pathogens hijack the endocytic machinery to deliver genetic material into the cell. Through computer simulation, we are able to perform detailed studies of the types of protein association pathways and their dependence on individual protein concentration that leads to clathrin coat formation. A long-term goal is to test the role of distinct cargo proteins in determining the successful nucleation and composition of the clathrin coat.
 


Selected Publications
Johnson, M.E., and G. Hummer. (2013) Evolutionary pressure ont he topology of protein interface interaction networks. J. Phys. Chem. B. (in press).

Johnson, M.E., and G. Hummer. (2013) Interface-resolved network of protein-protein interactions. PLoS Comput. Biol. 9:e1003065.

Johnson, M.E., and G. Hummer. (2012) Characterization of a dynamic string method for the construction of transition pathways in molecular systems. J. Phys. Chem. B. DOI: 10.1021/jp212611k.

Johnson, M.E., and G. Hummer. (2011) Nonspecific binding limits the number of proteins in a cell and shapes their interaction networks. Proc. Natl. Acad. Sci. USA 108:603-608.

Ponder, J.W., C.J. Wu, P.Y. Ren, V.S. Pande, J.D. Chodera, M.J. Schnieders, I. Haque, D.L. Mobley, D.S. Lambrecht, R.A. DiStasio, M. Head-Gordon, G.N.I. Clark, M.E. Johnson, and T. Head-Gordon. (2010) Current status of the AMOEBA polarizable force field. J. Phys. Chem. B. 114:2549-2564.

Johnson, M.E., C. Malardier-Jugroot, and T. Head-Gordon. (2010) Effects of co-solvents on peptide hydration water structure and dynamics. Phys. Chem. Chem. Phys. 12:393-405.

Malardier-Jugroot, C., D.T. Bowron, A.K. Soper, M.E. Johnson, and T. Head-Gordon. (2010) Structure and water dynamics of aqueous peptide solutions in the presence of co-solvents. Phys. Chem. Chem. Phys. 12:382-392.

Johnson, M.E., and T. Head-Gordon. (2009) Assessing thermodynamic-dynamic relationships for waterlike liquids. J. Chem. Phys. 130:214510.

Johnson, M.E., C. Malardier-Jugroot, R.K. Murarka, and T. Head-Gordon. (2009) Hydration water dynamics near biological interfaces. J. Phys. Chem. B. 113:4080-4092.

Malardier-Jugroot, C., M.E. Johnson, R.K. Murarka, and T. Head-Gordon. (2008) Aqueous peptides as experimental models for hydration water dynamics near protein surfaces. Phys. Chem. Chem. Phys. 10:4903-4908.

Johnson, M.E., T. Head-Gordon, and A.A. Louis. (2007) Representability problems for coarse-grained water potentials. J. Chem. Phys. 126:144509.

Head-Gordon, T., and M.E. Johnson. (2006) Tetrahedral structure or chains for liquid water. Proc. Natl. Acad. Sci. 103:7973-7977.

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