Multiscale models are important tools to elucidate how small changes in local subunit conformations may propagate to affect the properties of macromolecular complexes. We review recent advances in coarse-graining methods for poly-protein assemblies, systems that are composed of many copies of relatively few components, with a particular focus on viral capsids and cytoskeletal filaments. These methods are grouped into two broad categories-mapping methods, which use information from one scale of representation to parameterize a lower resolution model, and bridging methods, which repeatedly connect different scales during simulation-and we provide examples of both classes at different levels of complexity. Collectively, these models illustrate the numerous approaches to information transfer between scales and demonstrate that the complexity required of the model depends in general on the nature of the information sought.
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http://dx.doi.org/10.1016/j.sbi.2012.01.003 | DOI Listing |
J Chem Phys
November 2022
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.
The interior of living cells is densely filled with proteins and their complexes, which perform multitudes of biological functions. We use coarse-grained simulations to reach the system sizes and time scales needed to study protein complexes and their dense solutions and to interpret experiments. To take full advantage of coarse-graining, the models have to be efficiently implemented in simulation engines that are easy to use, modify, and extend.
View Article and Find Full Text PDFJ Am Soc Mass Spectrom
October 2017
Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
Multiprotein complexes are central to our understanding of cellular biology, as they play critical roles in nearly every biological process. Despite many impressive advances associated with structural characterization techniques, large and highly-dynamic protein complexes are too often refractory to analysis by conventional, high-resolution approaches. To fill this gap, ion mobility-mass spectrometry (IM-MS) methods have emerged as a promising approach for characterizing the structures of challenging assemblies due in large part to the ability of these methods to characterize the composition, connectivity, and topology of large, labile complexes.
View Article and Find Full Text PDFJ Mol Biol
April 2013
Department of Chemistry, James Franck Institute, Computation Institute, University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637, USA.
The actin regulatory protein cofilin plays a central role in actin assembly dynamics by severing filaments and increasing the concentration of ends from which subunits add and dissociate. Cofilin binding modifies the average structure and mechanical properties of actin filaments, thereby promoting fragmentation of partially decorated filaments at boundaries of bare and cofilin-decorated segments. Despite extensive evidence for cofilin-dependent changes in filament structure and mechanics, it is unclear how the two processes are linked at the molecular level.
View Article and Find Full Text PDFNucleic Acids Res
July 2012
Department of Nano Science and Technology and School of Mechanical Engineering, Sungkyunkwan University, 300, Cheoncheon-dong, Jangan-gu, Suwon 440-746, Korea.
KOSMOS is the first online morph server to be able to address the structural dynamics of DNA/RNA, proteins and even their complexes, such as ribosomes. The key functions of KOSMOS are the harmonic and anharmonic analyses of macromolecules. In the harmonic analysis, normal mode analysis (NMA) based on an elastic network model (ENM) is performed, yielding vibrational modes and B-factor calculations, which provide insight into the potential biological functions of macromolecules based on their structural features.
View Article and Find Full Text PDFCurr Opin Struct Biol
April 2012
Department of Chemistry, Institute for Biophysical Dynamics, James Franck Institute, and Computation Institute, University of Chicago, Chicago, IL 60637, United States.
Multiscale models are important tools to elucidate how small changes in local subunit conformations may propagate to affect the properties of macromolecular complexes. We review recent advances in coarse-graining methods for poly-protein assemblies, systems that are composed of many copies of relatively few components, with a particular focus on viral capsids and cytoskeletal filaments. These methods are grouped into two broad categories-mapping methods, which use information from one scale of representation to parameterize a lower resolution model, and bridging methods, which repeatedly connect different scales during simulation-and we provide examples of both classes at different levels of complexity.
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