Article thumbnail

Diffusion in crowded biological environments: applications of Brownian dynamics

By Maciej Długosz and Joanna Trylska


Biochemical reactions in living systems occur in complex, heterogeneous media with total concentrations of macromolecules in the range of 50 - 400 mgml. Molecular species occupy a significant fraction of the immersing medium, up to 40% of volume. Such complex and volume-occupied environments are generally termed 'crowded' and/or 'confined'. In crowded conditions non-specific interactions between macromolecules may hinder diffusion - a major process determining metabolism, transport, and signaling. Also, the crowded media can alter, both qualitatively and quantitatively, the reactions in vivo in comparison with their in vitro counterparts. This review focuses on recent developments in particle-based Brownian dynamics algorithms, their applications to model diffusive transport in crowded systems, and their abilities to reproduce and predict the behavior of macromolecules under in vivo conditions

Topics: Review
Publisher: BioMed Central
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1906). A new determinant of molecular dimension. Ann Physik
  2. (1997). An Expression for the Dispersion Force between Colloidal Particles.
  3. (2009). An O(N2) approximation for hydrodynamic interactions in Brownian dynamics simulations.
  4. (2008). AP: Macromolecular crowding and confinement: biochemical, biophysical and potential physiological consequences. Annu Rev Biophys
  5. (2006). Assessing implicit models for nonpolar mean solvation forces: The importance of dispersion and volume terms.
  6. (2003). Average hydrodynamic correction for the Brownian dynamics calculation of flocculation rates in concentrated dispersions. Phys Rev E
  7. (1988). Bossis G: Stokesian dynamics. Ann Rev Fluid Mech
  8. (1995). Brownian dynamics simulation of probe diffusion in DNA: effects of probe size, charge and DNA concentration. Bioph Chem
  9. (1996). Brownian dynamics simulation of the lateral distribution of charged membrane components. Eur Biophys J
  10. (1999). Brownian dynamics simulations of hard-sphere suspension.
  11. (1993). Brownian dynamics simulations of probe and self-diffusion in concentrated protein and DNA solutions.
  12. (1996). Brownian dynamics simulations of self and collective diffusion of near hard sphere colloidal liquids: inclusion of many-body hydrodynamics. Molec Phys
  13. (1999). Carrasco B: Calculation of NMR relaxation, covolume and scattering-related properties of bead-models using the SOLPRO computer program.
  14. (1986). Construction of Langevin forces in the simulation of hydrodynamic interaction. Macromolecules
  15. Crowding and hydrodynamic interactions likely dominate in vivo macromolecular motion.
  16. (2002). de la Torre JG: Brownian dynamics simulations of rigid particles of arbitrary shape in external fields.
  17. (1999). de la Torre JG: Hydrodynamic properties of rigid particles: comparison of different modeling and computational procedures.
  18. (2009). Description of nonspecific DNA-protein interaction and facilitated diffusion with a dynamical model.
  19. (2003). Diffusion in cells measured by fluorescence recovery after photobleaching. Method Enzymol
  20. (2009). Dynamical model of DNA-protein interaction: effect of protein charge distribution and mechanical properties.
  21. (2010). Elcock AH: Absolute protein-protein association rate constants from flexible, coarse-grained Brownian dynamics simulations: the role of intermolecular hydrodynamic interactions in barnase-barstar association.
  22. (2006). Elcock AH: Atomically detailed simulations of concentrated protein solutions: The effects of salt, pH, point mutations, and protein concentration in simulations of 1000-molecule systems.
  23. (2010). Elcock AH: Diffusion, crowding and protein stability in a dynamic molecular model of the bacterial cytoplasm. PLoS Comput Biol
  24. (2009). Elcock AH: Striking effects of hydrodynamic interactions on the simulated diffusion and folding of proteins.
  25. (2008). Ellison MJ: Coarse-grained molecular simulation of diffusion and reaction kinetics in a crowded virtual cytoplasm.
  26. (1986). Ewald sum of the Rotne-Prager tensor.
  27. (2010). F: Diffusion of α-chymotrypsin in solution-crowded media. A fluorescence recovery after photobleaching study.
  28. (2009). Fedotov VD: Brownian dynamics simulation of electrostatically interacting proteins. Mol Phys
  29. (2003). Helms V: Diffusional dynamics of cytochrome C molecules in the presence of a charged surface. Soft
  30. (1988). Honig B: Energetics of charge-charge interactions in proteins. Proteins: Struct Func Genet
  31. (2010). Hoshino M: Effects of macromolecular crowding on intracellular diffusion from a single particle perspective. Biophys Rev
  32. (1987). Hydrodynamic interactions in Brownian dynamics simulations. I. Periodic boundary conditions for computer simulations. Physica A
  33. (1985). JA: Brownian dynamics with rotationtranslation coupling.
  34. (1999). Leibler S: Protein mobility in the cytoplasm of Escherichia Coli.
  35. (2001). Macromolecular crowding: an important but neglected aspect of the intracellular environment. Curr Opin Struct Biol
  36. (1978). McCammon JA: Brownian dynamics with hydrodynamic interactions.
  37. (2001). McCammon JA: Calculation of weak protein-protein interactions: the pH dependence of the second virial coefficient.
  38. (1970). ML: Approximate methods of determining the double-layer free energy of interaction between two charged colloidal spheres.
  39. (2001). Modeling salt-mediated electrostatics of macromolecules: The discrete surface charge optimization algorithm and its application to the nucleosome. Biopolymers
  40. (2010). Models of macromolecular crowding effects and the need for quantitative comparisons with experiment. Curr Opin Struct Biol
  41. (2010). Nägele G: Generic behavior of the hydrodynamic function of charged colloidal suspensions.
  42. (2010). Nägele G: Long-time dynamics of concentrated chargestabilized colloids. Phys Rev Lett
  43. (2008). Nägele G: Short-time transport properties in dense suspensions: from neutral to charge-stabilized colloidal spheres.
  44. (1994). Oppenheim I: Dynamics of hard-sphere suspensions.
  45. (1971). Oppenheim I: Molecular theory of Brownian motion for several particles.
  46. (2010). Pielak GJ: A bioreactor for in-cell protein NMR.
  47. (2010). Pielak GJ: Volume exclusion and soft interaction effects on protein stability under crowded conditions. Biochemistry
  48. (2008). Probing the interior of living cells with fluorescence correlation spectroscopy.
  49. (1998). RC: Brownian dynamics simulation of proteinprotein diffusional encounter. Methods
  50. (1996). RC: Effective charges for macromolecules in solvent.
  51. (2010). Role of anisotropy for protein-protein encounter. Phys Rev E
  52. (1969). S: Variational treatment of hydrodynamic interaction in polymers.
  53. (2008). Schurtenberger P: A simple patchy colloid model for the phase behavior of lysozyme dispersions.
  54. (2008). Single molecule approach to molecular biology in living bacterial cells. Annu Rev Biophys
  55. (2005). Space in systems biology of signaling pathways - towards intracellular molecular crowding in silico.
  56. (2009). Stochastic simulation of signal transduction: impact on the cellular architecture on diffusion.
  57. (2001). The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media.
  58. (1948). The intrinsic viscosities and diffusion constants of flexible macromolecules in solution.
  59. (1937). The London -van der Waals attraction between spherical particles. Physica A
  60. (2007). Toward realistic modeling of dynamic processes in cell signaling: Quantification of macromolecular crowding effects.
  61. (1970). Transport properties of polymer chains in dilute solution: hydrodynamic interaction.
  62. (2003). Trizac E, Bocquet L: Effective charge versus bare charge: an analytical estimate for colloids in the infinite dilution limit.
  63. (1982). van Saarloos W: Many-sphere hydrodynamic interactions and mobilities in a suspension. Physica A
  64. (2008). Verkman AS: Crowding effects on diffusion in solutions and cells. Annu Rev Biophys
  65. (2007). Verkman AS: Single particle tracking of complex diffusion in membranes: simulation and detection of barrier, raft, and interaction phenomena.
  66. (2006). Weisshaar JC: Crowding and confinement effects on protein diffusionin vivo.
  67. (2010). Yethiraj A: Crowding effects on association reactions at membranes.
  68. (2009). Yethiraj A: Effect of macromolecular crowding on reaction rates: a computational study.
  69. (2008). Zielenkiewicz P: Influence of macromolecular crowding on protein-protein association rates - a Brownian dynamics study.
  70. (1981). Zimm BH: Monte Carlo approach to the analysis of the rotational diffusion of wormlike chains. Biopolymers