title: What determines protein folding type? An investigation of intrinsic structural properties and its implications for understanding folding mechanisms.
abstract: Protein folding experiments demonstrate that the folding behaviors of many proteins can be roughly classified into two types: two-state kinetics and multi-state kinetics. Although the two types of protein folding kinetics have been observed for a long time, what determines the folding type of a protein is still largely unclear. The present work performed a comparative study based on a dataset of 43 two-state and 42 multi-state folders at different levels of proteins' intrinsic properties from the simplest sequence length to native structure topology. The results show that protein's amino acids composition and the long-range interaction-based topological complexity rather than secondary structure contents are the major determinants of protein folding type. Furthermore, a sequence-based folding type prediction achieved an accuracy of more than 80%. These findings implicate that there is no clear boundary between secondary and tertiary structure formation during the protein folding process and support the existence of a continuum of folding mechanism between the two ends of hierarchic and nucleation folding scenarios.
authors.affiliation: Shandong Provincial Research Center for Bioinformatic Engineering and Technique, Center for Advanced Study, Shandong University of Technology, Zibo 255049, PR China. bgMa@sdut.edu.cn
authors.forename: Bin-Guang
authors.initials: BG
authors.lastname: Ma
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chen
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D008962:Models, Theoretical; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D011506:Proteins