English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Experiments and theories have shown that when steric interactions betweencrowding particles and proteins are dominant, which give rise to Asakura-Oosawadepletion forces, then the stabilities of the proteins increase compared to theinfinite dilution case. We show using theoretical arguments that the crowdervolume fraction ($\Phi_C$) dependent increase in the melting temperature ofglobular proteins, $\Delta T_m(\Phi_C) \approx \Phi_C^{\alpha}$ where $\alpha =\frac{1}{(3 \nu_{eff} - 1)}$. The effective Flory exponent, $\nu_{eff}$,relates the radius of gyration in the unfolded state to the number of aminoacid residues in the protein. We derive the bound 1.25 $\le \alpha \le$ 2.0.The theoretical predictions are confirmed using molecular simulations of$\lambda$ repressor in the presence of spherical crowding particles. Analysesof previous simulations and experiments confirm the predicted theoretical boundfor $\alpha$. We show that the non-specific attractions between crowdingparticles and amino acid residues have to be substantial to fully negate theenhanced protein stabilities due to intra protein attractive Asakura-Oosawa(AO) depletion potential. Using the findings, we provide an alternateexplanation for the very modest (often less than 0.5 Kcal/mol) destabilizationin certain proteins in the cellular milieu. Cellular environment ispolydisperse containing large and small crowding agents. AO arguments suggestthat proteins would be localized between large (sizes exceeding that of theproteins) crowders, which are predicted to have negligible effect on stability.{\it In vitro} experiments containing mixtures of crowding particles couldvalidate or invalidate the predictions.

Theory and simulations for crowding-induced changes in stability of proteins with applications to $\lambda$ repressor