Improved Gō-like models demonstrate the robustness of protein folding mechanisms towards non-native interactions.
The use of simple theoretical models has provided a considerable contribution to our present understanding of the means by which proteins adopt their native fold from the plethora of available unfolded states. A common assumption in building computationally tractable models has been the neglect of stabilizing non-native interactions in the class of models described as "Gō-like." The focus of this study is the characterization of the folding of a number of proteins via a Gō-like model, which aims to map a maximal amount of information reflecting the protein sequence onto a "minimalist" skeleton. This model is shown to contain sufficient information to reproduce the folding transition states of a number of proteins, including topologically analogous proteins that fold via different transition states. Remarkably, these models also demonstrate consistency with the general features of folding transition states thought to be stabilized by non-native interactions. This suggests that native interactions are the primary determinant of most protein folding transition states, and that non-native interactions lead only to local structural perturbations. A prediction is also included for an asymmetrical folding transition state of bacteriophage lambda protein W, which has yet to be subjected to experimental characterization.
Karanicolas
John
J
Department of Molecular Biology (TPC6), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Brooks
Charles L
CL
D019843:Archaeal Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D015678:Viral Structural Proteins / Q000737:chemistry / Q000378:metabolism
C408462:ACBP protein, Trypanosoma brucei; D019843:Archaeal Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015800:Protozoan Proteins; C093228:Sso7d protein, Sulfolobus; D015678:Viral Structural Proteins; C411883:protein W, bacteriophage lambda