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Examining the Self Assembly of the Villin Headpiece Protein: A Combined Experimental and Molecular Dynamics Study

ORAL

Abstract

The Villin Headpiece subdomain (VHP36) is a protein that is well studied experimentally and computationally such that its monomeric native structure and ability to self-assemble are well characterized. In this study, we present experimental evidence that VHP36 proteins in solution form a limited number of dimers while the large majority remain monomeric independent of concentration. We then use our in-house coarse-grain Discrete Molecular Dynamics (DMD) package DMD4B-HYDRA which combines discrete potential functionals with a four-bead protein model to observe VHP36 assembly in simulation. Dimers produced from the DMD simulations are converted from the four-bead model to an all-atom structure and their stability is analyzed via all-atom MD simulations in two frequently used MD force fields. Additional simulations of two unfolded VHP36 monomers are also simulated in the same MD force fields to observe the dimerization process in more detail. The purpose of this work is to assess and compare the ability of the MD force fields to capture the dimerization process and search for an explanation regarding the absence of larger order oligomers.

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Authors

  • Brian Andrews

    Drexel Univ

  • Anuradha Gupta

    New Jersey Inst of Tech, Pennsylvania State University, Bard College, University of Mississippi, Drexel Univ, Collaborator, University of Dayton, Morgan State University, Louisiana State University, University of Geneva, Instituto Superior Tecnico - Lisboa, Department of Biochemistry and Molecular Biology, Rutgers University, Institute for Quantitative Biomedicine, Rutgers University, Pennsylvania State University, and University of Illinois at Urbana-Champaign, University of Illinois at Urbana-Champaign, Department of Chemical Engineering, New Jersey Institute of Technology, Department of Physics and Astronomy, Rutgers University-New Brunswick, Department of Physics, Rutgers University, Max-Planck-Institut für Festkörperforschung, Heisenbergstrasse 1, 70569 Stuttgart, Germany, Department of Physics and Fribourg Center for Nanomaterials, University of Fribourg, Chemin du Musée 3, CH-1700 Fribourg, Switzerland, The MacDiarmid Institute for Advanced Materials and Nanotechnology, 1010 Auckland, New Zealand, Department of Physics, College of William & Mary, Williamsburg, VA 23187-8795, USA, New Jersey Institute of Technology, Newark, NJ, USA, University of California, Los Angeles, CA, USA, University of California, Berkeley, CA, USA, Space Research Institute of RAS, Moscow, Russia, Georgetown University, Institut Polytechnique de Paris, University of Delaware, Brookhaven National Laboratory, San Diego State University, University of Chicago, University of Illinois at Chicago, Argonne National Laboratory, Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854, USA, University of Washington

  • Brigita Urbanc

    Drexel Univ, Drexel University