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Journal of Molecular Modeling

, Volume 17, Issue 1, pp 37–48 | Cite as

Structure and dynamics of human vimentin intermediate filament dimer and tetramer in explicit and implicit solvent models

  • Zhao Qin
  • Markus J. Buehler
Original Paper

Abstract

Intermediate filaments, in addition to microtubules and microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells, and play an important role in mechanotransduction as well as in providing mechanical stability to cells at large stretch. The molecular structures, mechanical and dynamical properties of the intermediate filament basic building blocks, the dimer and the tetramer, however, have remained elusive due to persistent experimental challenges owing to the large size and fibrillar geometry of this protein. We have recently reported an atomistic-level model of the human vimentin dimer and tetramer, obtained through a bottom-up approach based on structural optimization via molecular simulation based on an implicit solvent model (Qin et al. in PLoS ONE 2009 4(10):e7294, 9). Here we present extensive simulations and structural analyses of the model based on ultra large-scale atomistic-level simulations in an explicit solvent model, with system sizes exceeding 500,000 atoms and simulations carried out at 20 ns time-scales. We report a detailed comparison of the structural and dynamical behavior of this large biomolecular model with implicit and explicit solvent models. Our simulations confirm the stability of the molecular model and provide insight into the dynamical properties of the dimer and tetramer. Specifically, our simulations reveal a heterogeneous distribution of the bending stiffness along the molecular axis with the formation of rather soft and highly flexible hinge-like regions defined by non-alpha-helical linker domains. We report a comparison of Ramachandran maps and the solvent accessible surface area between implicit and explicit solvent models, and compute the persistence length of the dimer and tetramer structure of vimentin intermediate filaments for various subdomains of the protein. Our simulations provide detailed insight into the dynamical properties of the vimentin dimer and tetramer intermediate filament building blocks, which may guide the development of novel coarse-grained models of intermediate filaments, and could also help in understanding assembly mechanisms.

Keywords

Bending stiffness Biopolymer Dimer Explicit solvent Implicit solvent Intermediate filaments Materiomics Molecular dynamics Molecular structure Persistence length Structural optimization Tetramer Vimentin 

Notes

Acknowledgments

ZQ and MJB acknowledge support by Air Force Office of Scientific Research (AFOSR) (FA9550-08-1-0321) and National Science Foundation (NSF) (MRSEC DMR-081976). This research was supported by an allocation of advanced computing resources supported by the National Science Foundation (TeraGrid, grant # TG-MSS080030). The authors acknowledge support from the TeraGrid Advanced Support Program. The authors declare no conflict of interest of any sort.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Center for Materials Science and EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Center for Computational EngineeringMassachusetts Institute of TechnologyCambridgeUSA

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