Book of Abstracts: Albany 2007
June 19-23 2007
Computational Models of Chaperonin-mediated Protein Folding
Chaperonins are biological nanomachines that assist protein folding under non-permissive conditions. During the chaperonin cycle, concerted, large scale, rigid body conformational changes, ultimately driven by ATP hydrolysis, result in a dramatically expanded chaperonin cavity serving as folding chamber. Chaperonins repeatedly bind misfolded proteins, randomly disrupt their structure, and release them in less folded states, allowing these substrate proteins multiple opportunities to find pathways leading to the native state. To study the chaperonin annealing action we performed coarse-grained molecular dynamics simulations. We find that the fundamental annealing function of the GroEL chaperonin consists of forced unfolding and refolding of the substrate protein. The annealing action is related to the change in the nature of the interaction between the substrate protein and the GroEL particle from predominantly hydrophobic to largely hydrophilic. We also propose a bioinformatic method to identify natural GroEL substrates. Our hypothesis is that natural substrates contain patterns of residues similar to those in the co-chaperonin GroES. To validate this criterion we have employed a database of 252 proteins that have been experimentally shown to interact with the chaperonin machinery in vivo. More than 80% of these proteins are identified as substrates by our criterion.
1Department of Chemistry