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Transfer Free Energies of Test Proteins Into Crowded Protein Solutions Have Simple Dependence on Crowder Concentration.

ABSTRACT: The effects of macromolecular crowding on the thermodynamic properties of test proteins are determined by the latter's transfer free energies from a dilute solution to a crowded solution. The transfer free energies in turn are determined by effective protein-crowder interactions. When these interactions are modeled at the all-atom level, the transfer free energies may defy simple predictions. Here we investigated the dependence of the transfer free energy (??) on crowder concentration. We represented both the test protein and the crowder proteins atomistically, and used a general interaction potential consisting of hard-core repulsion, non-polar attraction, and solvent-screened electrostatic terms. The chemical potential was rigorously calculated by FMAP (Qin and Zhou, 2014), which entails expressing the protein-crowder interaction terms as correlation functions and evaluating them via fast Fourier transform (FFT). To high accuracy, the transfer free energy can be decomposed into an excluded-volume component (??_e-v), arising from the hard-core repulsion, and a soft-attraction component (??_s-a), arising from non-polar and electrostatic interactions. The decomposition provides physical insight into crowding effects, in particular why such effects are very modest on protein folding stability. Further decomposition of ??_s-a into non-polar and electrostatic components does not work, because these two types of interactions are highly correlated in contributing to ??_s-a. We found that ??_e-v fits well to the generalized fundamental measure theory (Qin and Zhou, 2010), which accounts for atomic details of the test protein but approximates the crowder proteins as spherical particles. Most interestingly, ??_s-a has a nearly linear dependence on crowder concentration. The latter result can be understood within a perturbed virial expansion of ?? (in powers of crowder concentration), with ??_e-v as reference. Whereas the second virial coefficient deviates strongly from that of the reference system, higher virial coefficients are close to their reference counterparts, thus leaving the linear term to make the dominant contribution to ??_s-a.

SUBMITTER: Nguemaha V

PROVIDER: S-EPMC6549383 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Transfer Free Energies of Test Proteins Into Crowded Protein Solutions Have Simple Dependence on Crowder Concentration.

Nguemaha Valery V Qin Sanbo S Zhou Huan-Xiang HX

Frontiers in molecular biosciences 20190529

The effects of macromolecular crowding on the thermodynamic properties of test proteins are determined by the latter's transfer free energies from a dilute solution to a crowded solution. The transfer free energies in turn are determined by effective protein-crowder interactions. When these interactions are modeled at the all-atom level, the transfer free energies may defy simple predictions. Here we investigated the dependence of the transfer free energy (Δμ) on crowder concentration. We repres ...[more]

PMID: 31192219

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Project description:ObjectiveThe goal of this work is to provide temperature and concentration calibration of water diffusivity in polyvinylpyrrolidone (PVP) solutions used in phantoms to assess system bias and linearity in apparent diffusion coefficient (ADC) measurements.MethodADC measurements were performed for 40 kDa (K40) PVP of six concentrations (0%, 10%, 20%, 30%, 40%, and 50% by weight) at three temperatures (19.5°C, 22.5°C, and 26.4°C), with internal phantom temperature monitored by optical thermometer (±0.2°C). To achieve ADC measurement and fit accuracy of better than 0.5%, three orthogonal diffusion gradients were calibrated using known water diffusivity at 0°C and system gradient nonlinearity maps. Noise-floor fit bias was also controlled by limiting the maximum b-value used for ADC calculation of each sample. The ADC temperature dependence was modeled by Arrhenius functions of each PVP concentration. The concentration dependence was modeled by quadratic function for ADC normalized by the theoretical water diffusion values. Calibration coefficients were obtained from linear regression model fits.ResultsMeasured phantom ADC values increased with temperature and decreasing PVP concentration, [PVP]. The derived Arrhenius model parameters for [PVP] between 0% and 50%, are reported and can be used for K40 ADC temperature calibration with absolute ADC error within ±0.016 μm2 /ms. Arrhenius model fit parameters normalized to water value scaled with [PVP] between 10% and 40%, and proportional change in activation energy increased faster than collision frequency. ADC normalization by water diffusivity, DW , from the Speedy-Angell relation accounted for the bulk of temperature dependence (±0.035 μm2 /ms) and yielded quadratic calibration for ADCPVP /DW = (12.5 ± 0.7) ·10-5 ·[PVP]2 - (23.2 ± 0.3)·10-3 ·[PVP]+1, nearly independent of PVP molecular weight and temperature.ConclusionThe study provides ground-truth ADC values for K40 PVP solutions commonly used in diffusion phantoms for scanning at ambient room temperature. The described procedures and the reported calibration can be used for quality control and standardization of measured ADC values of PVP at different concentrations and temperatures.

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Transfer Free Energies of Test Proteins Into Crowded Protein Solutions Have Simple Dependence on Crowder Concentration.

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Transfer Free Energies of Test Proteins Into Crowded Protein Solutions Have Simple Dependence on Crowder Concentration.

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