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Quantifying protein-protein association rate in polymer solutions: crowding-induced diffusion and energy modifications

Abstract

A theoretical framework is developed to study the protein-protein association in polymer solutions within diffusion-limited assumption. Starting from the basal association rate, two fundamental aspects concerning macromolecular crowding are particularly taken into account. One is the effect of microviscosity subject to protein diffusion. The length-scale dependent relations of translational and rotational diffusion coefficients are incorporated. Another is relevant to the crowding-induced effective interaction between the pair of proteins. The resultant energy modifications to the basal association rate are properly introduced, following an instructive classification with crowder size increasing: repulsive interaction dominant, repulsive and attractive interactions competitive, and attractive interaction prevailing. With specific energy modification terms, we are able to investigate the deviations of association rate from the Stokes-Einstein (SE) behavior (i.e., the linear relationship with respect to the reciprocal of macroviscosity) in a quantitative manner. Our theory is applied to study the association of TEM1-β-lactamase (TEM) and β-lactamase inhibitor protein (BLIP) in polyethylene glycol (PEG) solutions, with varying concentration and polymerization. We explicitly evaluate the relative association rate constant as a function of the solution macroviscosity. The theoretical results demonstrate a very good agreement with the experimental data. Moreover, the complicated non-trivial deviations, either positive (slower than SE) or negative (faster than SE), are systematically rationalized. The very role of energy modifications as well as the microviscosity effect on diffusion, in particular on rotational diffusion, is clearly unraveled.

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Publication details

The article was received on 15 Aug 2018, accepted on 09 Oct 2018 and first published on 12 Oct 2018


Article type: Paper
DOI: 10.1039/C8CP05203D
Citation: Phys. Chem. Chem. Phys., 2018, Accepted Manuscript
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    Quantifying protein-protein association rate in polymer solutions: crowding-induced diffusion and energy modifications

    J. Qing, A. Chen and N. Zhao, Phys. Chem. Chem. Phys., 2018, Accepted Manuscript , DOI: 10.1039/C8CP05203D

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