Stability of a protein tethered to a surface.
Surface-tethered proteins are increasingly being used in a variety of experimental situations, and they are the basis for many new technologies. Nevertheless, a thorough understanding of how a surface can impact the native state stability of an attached protein is lacking. In this work, the authors use molecular dynamics simulations of a model beta-barrel protein to investigate how surface tethering influences native state stability. They find that stability, as measured by the folding temperature Tf, can be either increased, decreased, or remain unchanged as a result of tethering. Observed shifts are highly dependent on the location of residue used as the tether point, and stability is influenced by a number of factors, both energetic and entropic. These factors include native state vibrations, loss of bulk unfolded conformations, changes to the unfolded state ensemble, and the emergence of an entropic term not present for the bulk protein. They discuss each of these contributions in detail and comment on their relative importance and connection to experiment.
Friedel
Miriam
M
Department of Physics, University of California, Santa Barbara, California 93106, USA.
Baumketner
Andrij
A
Shea
Joan-Emma
JE
D000327:Adsorption; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D008956:Models, Chemical; D011506:Proteins / Q000737:chemistry*
D011506:Proteins