Biochemical effects of molecular crowding

The cell cytoplasm is a dense environment where the presence of inert cosolutes can significantly alter the rates of protein folding and protein association reactions. Most theoretical studies focus on hard sphere crowding agents and quantify the effect of excluded volume on reaction rates. In this work the effect of interactions between the crowding agents on the thermodynamics of protein association is studied using computer simulation. Three cases are considered, where the crowding agents are (i) hard spheres, (ii) hard spheres with additional attractive or repulsive interactions, and (iii) chains of hard spheres. Reactants and products of the protein association are modeled as hard spheres. Although crowding effects are sensitive to the shape of the reaction product, in most cases the excess free energy difference between the product and reactants (nonideality factor) is insensitive to the interactions between crowding agents, due to a cancellation of effects. The simulations therefore suggest that the hard sphere model of crowding agents has a surprisingly large regime of validity and should be sufficient for a qualitative understanding of the thermodynamics of crowding effects when the interactions of associating proteins with crowding agents other than excluded volume interactions are not significant.

Crowding

Macromolecular Crowding

Hard spheres

Excluded volume

Inert

10.1021/jp107123y

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Citations (36)

Beyond the Excluded Volume Effects: Mechanistic Complexity of the Crowded Milieu

Molecules (2015)

Irina М. Kuznetsova Boris Y. Zaslavsky Leonid Breydo Konstantin К. Turoverov Vladimir N. Uversky

Macromolecular crowding is known to affect protein folding, binding of small molecules, interaction with nucleic acids, enzymatic activity, protein-protein interactions, and protein aggregation. Although for a long time it was believed that the major mechanism of the action of crowded environments on structure, folding, thermodynamics, and function of a protein can be described in terms of the excluded volume effects, it is getting clear now that other factors originating from the presence of high concentrations of “inert” macromolecules in crowded solution should definitely be taken into account to draw a more complete picture of a protein in a crowded milieu. This review shows that in addition to the excluded volume effects important players of the crowded environments are viscosity, perturbed diffusion, direct physical interactions between the crowding agents and proteins, soft interactions, and, most importantly, the effects of crowders on solvent properties.

Macromolecular Crowding

Excluded volume

Folding (DSP implementation)

Macromolecular Substances

Crowding

10.3390/molecules20011377

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Citations (189)

Connecting the Dots: Macromolecular Crowding and Protein Aggregation

Journal of Fluorescence (2022)

Gufran Ahmed Siddiqui Aabgeena Naeem

Macromolecular Crowding