The effect of surface tethering on the folding of the src-SH3 protein domain.
The effect of surface tethering on the folding mechanism of the src-SH3 protein domain was investigated using a coarse-grained Gō-type protein model. The protein was tethered at various locations along the protein chain and the thermodynamics and kinetics of folding were studied using replica exchange and constant temperature Langevin dynamics. Our simulations reveal that tethering in a structured part of the transition state can dramatically alter the folding mechanism, while tethering in an unstructured part leaves the folding mechanism unaltered as compared to bulk folding. Interestingly, there is only modest correlation between the tethering effect on the folding mechanism and its effect on thermodynamic stability and folding rates. We suggest locations on the protein at which tethering could be performed in single-molecule experiments so as to leave the folding mechanism unaltered from the bulk.
Zhuang
Zhuoyun
Z
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106-9510, USA.
Jewett
Andrew I
AI
Soto
Patricia
P
Shea
Joan-Emma
JE
D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics; D018909:src Homology Domains
D011506:Proteins