Flexibility of the bacterial chaperone trigger factor in microsecond-timescale molecular dynamics simulations.
The bacterial chaperone trigger factor (TF) is the first chaperone to be encountered by a nascent protein chain as it emerges from the ribosome exit tunnel. Experimental results suggest that TF possesses considerable conformational flexibility, and in an attempt to provide an atomic-level view of this flexibility, we have performed independent 1.5-μs molecular dynamics simulations of TF in explicit solvent using two different simulation force fields (OPLS-AA/L and AMBER ff99SB-ILDN). Both simulations indicate that TF possesses tremendous flexibility, with huge excursions from the crystallographic conformation caused by reorientations of the protein's constituent domains; both simulations also predict the formation of extensive contacts between TF's PPIase domain and the Arm 1 domain that is involved in nascent-chain binding. In the OPLS simulation, however, TF rapidly settles into a very compact conformation that persists for at least 1 μs, whereas in the AMBER simulation, it remains highly dynamic; additional simulations in which the two force fields were swapped suggest that these differences are at least partly attributable to sampling issues. The simulation results provide potential rationalizations of a number of experimental observations regarding TF's conformational behavior and have implications for using simulations to model TF's function on translating ribosomes.
Department of Biochemistry, University of Iowa, Iowa City, USA.
Andrew S
AS
Thomas
Suifang
S
Mao
Adrian H
AH
Elcock
D000595:Amino Acid Sequence; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D029968:Escherichia coli Proteins; C403324:trigger factor, E coli; D019696:Peptidylprolyl Isomerase