a didactic model of macromolecular crowding effects on protein folding大分子拥挤的说教的模型对蛋白质折叠的影响.pdfVIP

A Didactic Model of Macromolecular Crowding Effects on Protein Folding 1 2 3 Douglas Tsao , Allen P. Minton , Nikolay V. Dokholyan * 1 Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, United States of America, 2 Section on Physical Biochemistry, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland, United States of America, 3 Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America 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. Citation: Tsao D, Minton AP, Dokholyan NV (2010) A Didactic Model of Macromolecular Crowding Effects on Protein Folding. PLoS ONE 5(8): e11936. doi:10.1371/ journal.pone.0011936 Editor: Andreas