Hydrodynamic Properties of Biomacromolecules and Macromolecular Complexes: Concepts and Methods. A Tutorial Mini-review

• Published in: Journal of molecular biology 2020-04, Vol.432 (9), p.2930-2948
• Main Authors: García de la Torre, J., Hernández Cifre, J.G.
• Format: Article
• Language: English
• Subjects: Brownian dynamics; disordered proteins; hydrodynamic models and calculations; solution properties
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2019.12.027

This article is intended to be an overview of the current possibilities offered by hydrodynamic methods in the calculation of properties and prediction of the behavior of biomacromolecules in solution. First, we briefly cover the experimental techniques, mentioning their fundamentals and current status. Using a tutorial approach, we provide basic hints to understand conceptual aspects of macromolecular hydrodynamics which underlie the instrumental methods and the modeling and computational procedures. The description is focused on the bead model methodology as implemented in the HYDRO suite of computer programs. For rigid particles, we cover simple models, such as ellipsoids and cylinders, to the most detailed models with atomic resolution. The fundamentals and applicability of the basic random coil and wormlike models for flexible particles are also briefly described. In addition to the simple linear, more or less flexible chain, flexibility may appear in other more specific forms. These cases can be treated by Monte Carlo and Brownian simulation methods, for which computational tools are also available. Finally, we present in some detail the applicability of these tools for unfolded and intrinsically disordered proteins. For the particular case of partially disordered proteins comprising both globular domains and flexible linkers or tails, solution properties can be accurately predicted, and this validation makes the methodology quite promising for future work. [Display omitted] •Knowledge of macromolecular hydrodynamics is required for a proper use of instrumental techniques and computational tools.•Hydrodynamic models and computational tools are available to capture from overall macromolecular shape to atomic details.•Accuracy of computation and experiments sets a limit on the confidence on the agreement between models and experiments.•Monte Carlo and Brownian dynamics capture the complicated conformational variability of flexible macromolecules.•Monte Carlo and Brownian dynamics are valuable to describe properties of intrinsically disordered proteins.