title: Crowding effects on protein association: effect of interactions between crowding agents.
abstract: 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.
authors.affiliation: Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Arun
authors.initials: A
authors.lastname: Yethiraj
mesh_terms: D003198:Computer Simulation; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008962:Models, Theoretical; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011108:Polymers; D011506:Proteins