title: A didactic model of macromolecular crowding effects on protein folding.
abstract: A didactic model is presented to illustrate how the effect of macromolecular crowding on protein folding and association is modeled using current analytical theory and discrete molecular dynamics. While analytical treatments of crowding may consider the effect as a potential of average force acting to compress a polypeptide chain into a compact state, the use of simulations enables the presence of crowding reagents to be treated explicitly. Using an analytically solvable toy model for protein folding, an approximate statistical thermodynamic method is directly compared to simulation in order to gauge the effectiveness of current analytical crowding descriptions. Both methodologies are in quantitative agreement under most conditions, indication that both current theory and simulation methods are capable of recapitulating aspects of protein folding even by utilizing a simplistic protein model.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Douglas
authors.initials: D
authors.lastname: Tsao
authors.forename: Allen P
authors.initials: AP
authors.lastname: Minton
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
mesh_terms: D004305:Dose-Response Relationship, Drug; D056004:Molecular Dynamics Simulation; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*; D012399:Rotation; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology
chemical_list: D011506:Proteins; D014508:Urea