TY - JOUR
T1 - Building Structural Models of a Whole Mycoplasma Cell
AU - Maritan, Martina
AU - Autin, Ludovic
AU - Karr, Jonathan
AU - Covert, Markus W.
AU - Olson, Arthur J.
AU - Goodsell, David S.
N1 - Funding Information:
We thank Michel Sanner, Stefano Forli, and Andrew Jewett for helpful discussions and Jerome Eberhardt for coding support. We thank the SWISS-MODEL team and Prof. McGuffin for running modeling predictions on their local servers. This work was supported by NIH R01 GM120604 (DSG), R35 GM119771 (JK), and an Allen Discovery Center award from the Paul G. Allen Family Foundation (MWC). This is manuscript 30120 from the Scripps Research Institute. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Funding Information:
We thank Michel Sanner, Stefano Forli, and Andrew Jewett for helpful discussions and Jerome Eberhardt for coding support. We thank the SWISS-MODEL team and Prof. McGuffin for running modeling predictions on their local servers. This work was supported by NIH R01 GM120604 (DSG), R35 GM119771 (JK), and an Allen Discovery Center award from the Paul G. Allen Family Foundation (MWC). This is manuscript 30120 from the Scripps Research Institute.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/1/30
Y1 - 2022/1/30
N2 - 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.
AB - 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.
KW - computational modeling
KW - mycoplasma genitalium
KW - nucleoid structure
KW - scientific visualization
KW - whole cell modeling
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U2 - 10.1016/j.jmb.2021.167351
DO - 10.1016/j.jmb.2021.167351
M3 - Article
C2 - 34774566
AN - SCOPUS:85119403137
VL - 434
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 2
M1 - 167351
ER -