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Building Structural Models of a Whole Mycoplasma Cell
Institution:1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037 USA;2. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;3. Department of Bioengineering, Stanford University, Stanford, CA 94305, USA;4. RCSB Protein Data Bank and Institute for Quantitative Biomedicine, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA;1. Protein Analysis Group, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen Ø, Denmark;2. Laboratory for Membrane Protein Dynamics, Department of Neuroscience, University of Copenhagen, 2200 Copenhagen N, Denmark;1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA;2. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA;3. Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, 00014 Helsinki, Finland;1. Center for the Physics of Living Cells, University of Illinois, Urbana, Illinois;2. Department of Physics, University of Illinois, Urbana, Illinois;3. Department of Chemistry, University of Illinois, Urbana, Illinois;4. Department of Bioengineering, University of California, San Diego, La Jolla, California;5. School of Chemical Sciences, University of Illinois, Urbana, Illinois;6. Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California;7. Department of Chemistry, Scripps Research Institute, La Jolla, California;8. Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, California;1. Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark;2. Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, 2100 Copenhagen, Denmark;3. Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Boulevard, Pasadena, CA 91125, USA;4. Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544, USA;1. Department of Chemistry, University of Illinois at Urbana-Champaign, USA;2. Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA;3. Center for the Physics of the Living Cell, University of Illinois at Urbana-Champaign, USA
Abstract:Building structural models of entire cells has been a long-standing cross-discipline challenge for the research community, as it requires an unprecedented level of integration between multiple sources of biological data and enhanced methods for computational modeling and visualization. Here, we present the first 3D structural models of an entire Mycoplasma genitalium (MG) cell, built using the CellPACK suite of computational modeling tools. Our model recapitulates the data described in recent whole-cell system biology simulations and provides a structural representation for all MG proteins, DNA and RNA molecules, obtained by combining experimental and homology-modeled structures and lattice-based models of the genome. We establish a framework for gathering, curating and evaluating these structures, exposing current weaknesses of modeling methods and the boundaries of MG structural knowledge, and visualization methods to explore functional characteristics of the genome and proteome. We compare two approaches for data gathering, a manually-curated workflow and an automated workflow that uses homologous structures, both of which are appropriate for the analysis of mesoscale properties such as crowding and volume occupancy. Analysis of model quality provides estimates of the regularization that will be required when these models are used as starting points for atomic molecular dynamics simulations.
Keywords:whole cell modeling  computational modeling  nucleoid structure  scientific visualization  mycoplasma genitalium  MG"}  {"#name":"keyword"  "$":{"id":"pc_XYfdIxNZcb"}  "$$":[{"#name":"text"  "$$":[{"#name":"italic"  "_":"Mycoplasma genitalium  WC-MG"}  {"#name":"keyword"  "$":{"id":"pc_D7kSNaokwk"}  "$$":[{"#name":"text"  "_":"Previously reported WholeCell model of MG  3D-WC-MG"}  {"#name":"keyword"  "$":{"id":"pc_ulBOUB6xrh"}  "$$":[{"#name":"text"  "_":"Three-dimensional model of MG reported here  CYT-MG"}  {"#name":"keyword"  "$":{"id":"pc_qfBdKTGC36"}  "$$":[{"#name":"text"  "_":"Previously reported model of MG cytoplasm
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