Analysis of multiple folding routes of proteins by a coarse-grained dynamics model
Erman, Burak (2001) Analysis of multiple folding routes of proteins by a coarse-grained dynamics model. Biophysical Journal, 81 (6). pp. 3534-3544. ISSN 0006-3495 (Print) 1542-0086 (Online)
Official URL: http://dx.doi.org/10.1016/S0006-3495(01)75984-X
Langevin dynamics of a protein molecule with Go-type potentials is developed and used to analyze long time-scale events in the folding of cytochrome c. Several trajectories are generated, starting from random coil configurations and going to the native state, that are a few angstroms root mean square deviation (RMSD) from the native structure. The dynamics is controlled, to a large scale, by the two terminal helices that are in contact in the native state. These two helices form very early during folding, and depending on the trajectory, they either stabilize rapidly or break and re-form in going over steric barriers. The extended initial chain exhibits a rapid folding transition into a relatively compact shape, after which the helices are reorganized in a highly correlated manner. The time of formation of residue pair contacts strongly points to the hierarchical nature of folding; i.e., secondary structure forms first, followed by rearrangements of larger length scales at longer times. The kinetics of formation of native contacts is also analyzed, and the onset of a stable globular configuration, referred to as the molten globule in the literature, is identified. Predictions of the model are compared with extensive experimental data on cytochrome c.
Repository Staff Only: item control page