on the origins of the weak folding cooperativity of a designed ββα ultrafast protein fsd-1的起源弱折叠的协同设计ββαfsd-1超速的蛋白质.pdfVIP

On the Origins of the Weak Folding Cooperativity of a Designed bba Ultrafast Protein FSD-1 1 1,2 Chun Wu , Joan-Emma Shea * 1 Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California, United States of America, 2 Department of Physics, University of California, Santa Barbara, Santa Barbara, California, United States of America Abstract FSD-1, a designed small ultrafast folder with a bba fold, has been actively studied in the last few years as a model system for studying protein folding mechanisms and for testing of the accuracy of computational models. The suitability of this protein to describe the folding of naturally occurring a/ b proteins has recently been challenged based on the observation that the melting transition is very broad, with ill-resolved baselines. Using molecular dynamics simulations with the AMBER protein force field (ff96) coupled with the implicit solvent model (IGB = 5), we shed new light into the nature of this transition and resolve the experimental controversies. We show that the melting transition corresponds to the melting of the protein as a whole, and not solely to the helix-coil transition. The breadth of the folding transition arises from the spread in the melting temperatures (from ,325 K to ,302 K) of the individual transitions: formation of the hydrophobic core, b-hairpin and tertiary fold, with the helix formed earlier. Our simulations initiated from an extended chain accurately predict the native structure, provide a reasonable estimate of the transition barrier height, and explicitly demonstrate the existence of multiple pathways and multiple transition states for folding. Our exhaustive sampling enables us to assess the quality of the Amber ff96/igb