Dynamic cluster formation determines viscosity and diffusion in dense protein solutions.
MD simulation
diffusion
dynamic clusters
protein crowding
viscosity
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
14 05 2019
14 05 2019
Historique:
pubmed:
1
5
2019
medline:
27
3
2020
entrez:
1
5
2019
Statut:
ppublish
Résumé
We develop a detailed description of protein translational and rotational diffusion in concentrated solution on the basis of all-atom molecular dynamics simulations in explicit solvent. Our systems contain up to 540 fully flexible proteins with 3.6 million atoms. In concentrated protein solutions (100 mg/mL and higher), the proteins ubiquitin and lysozyme, as well as the protein domains third IgG-binding domain of protein G and villin headpiece, diffuse not as isolated particles, but as members of transient clusters between which they constantly exchange. A dynamic cluster model nearly quantitatively explains the increase in viscosity and the decrease in protein diffusivity with protein volume fraction, which both exceed the predictions from widely used colloid models. The Stokes-Einstein relations for translational and rotational diffusion remain valid, but the effective hydrodynamic radius grows linearly with protein volume fraction. This increase follows the observed increase in cluster size and explains the more dramatic slowdown of protein rotation compared with translation. Baxter's sticky-sphere model of colloidal suspensions captures the concentration dependence of cluster size, viscosity, and rotational and translational diffusion. The consistency between simulations and experiments for a diverse set of soluble globular proteins indicates that the cluster model applies broadly to concentrated protein solutions, with equilibrium dissociation constants for nonspecific protein-protein binding in the K
Identifiants
pubmed: 31036655
pii: 1817564116
doi: 10.1073/pnas.1817564116
pmc: PMC6525548
doi:
Substances chimiques
Colloids
0
Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9843-9852Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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