Methods and Tools for the Prediction of Hydrodynamic Coefficients and Other Solution Properties of Flexible Macromolecules in Solution. A Tutorial Minireview

Abstract

The calculation of solution properties of flexible macromolecules and other nanoparticles requires, in addition to the hydrodynamic formalisms needed for the sedimentation coefficient and other transport properties, the consideration of the conformational statistics and internal dynamics. The latter aspects can be handled with simulation methods like Monte Carlo and Brownian dynamics. An example of a Monte Carlo simulation for a model specific of DNA is illustrated with results for the several solution properties over an extremely wide range of molecular weight. The convenience of having computational tools of a quite general applicability has prompted us to implement the simulation and hydrodynamic treatments in software packages, MONTEHYDRO for Monte Carlo, and SIMUFLEX for Brownian dynamics which-with a scope similar to the HYDRO suite for rigid particles-can handle a variety of situations. As an application of the new methodology to a yet unclear problem in analytical ultracentrifugation, in a simple application of the SIMUFLEX software, we present a simulation of the so-called anomalous sedimentation of very long DNA molecules, obtaining results for the experimentally observable rotor-speed-dependence of the sedimentation coefficient.

Hydrodynamic and Electrophoretic Properties of Trastuzumab/HER2 Extracellular Domain Complexes as Revealed by Experimental Techniques and Computational Simulations

“…This methodology to obtain hydrodynamic properties as conformational averages of values computed from conformations generated in a non-hydrodynamic simulation, in our case from MD simulations, is the so-called rigid-body approximation. This procedure has been provided to be nearly exact for macromolecules with localized (segmental) flexibility [75].…”

Viscosity and diffusion: crowding and salt effects in protein solutions

“…Crystallographic measurements [28][29][30] have revealed a flat and roughly heartshaped structure of albumins. The computation of singleparticle properties with an account of the highly complex particle shape of biomolecules can be done by numerical simulations only and is beyond the scope of this paper [29,31]. Rather, the aim of the present study is to give an essentially analytic description of the microstructure and the dynamics of interacting BSA proteins with low computational cost.…”

“…The computation of single-particle properties with an account of the highly complex particle shape of biomolecules can be done by numerical simulations only and is beyond the scope of this paper. 43,45 Rather, the aim of the present study is to give an essentially analytic description of the microstructure and the dynamics of interacting BSA proteins with low computational cost. We therefore intentionally choose an extremely simple model for the fit of the protein form factor, by an oblate, solid ellipsoid (spheroid).…”

A database of calculated solution parameters for the recently released AlphaFold predicted protein structures

“…Here the US-SOMO-AF database can only raise red flags, such as very high predicted [η] values associated with visualized extended, unstructured parts. Dealing with these issues requires much longer calculations involving either Monte Carlo methods or Brownian dynamics simulations (see 39 ), that would require a major effort to be applied systematically on >365,000 structures.…”