Molecular simulations of cotranslational protein folding: fragment stabilities, folding cooperativity, and trapping in the ribosome.

ABSTRACT: Although molecular simulation methods have yielded valuable insights into mechanistic aspects of protein refolding in vitro, they have up to now not been used to model the folding of proteins as they are actually synthesized by the ribosome. To address this issue, we report here simulation studies of three model proteins: chymotrypsin inhibitor 2 (CI2), barnase, and Semliki forest virus protein (SFVP), and directly compare their folding during ribosome-mediated synthesis with their refolding from random, denatured conformations. To calibrate the methodology, simulations are first compared with in vitro data on the folding stabilities of N-terminal fragments of CI2 and barnase; the simulations reproduce the fact that both the stability and thermal folding cooperativity increase as fragments

SUBMITTER: Elcock AH 

PROVIDER: S-EPMC1523309 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature