title: Identifying folding nucleus based on residue contact networks of proteins.
abstract: In the native structure of a protein, all the residues are tightly parked together in a specific order following its folding and every residue contacts with some spatially neighbor residues. A residue contact network can be constructed by defining the residues as nodes and the native contacts as edges. During the folding of small single-domain proteins, there is a set of contacts (or bonds), defined as the folding nucleus (FN), which is formed around the transition state, i.e., a rate-limiting barrier located at about the middle between the unfolded states and the native state on the free energy landscape. Such a FN plays an essential role in the folding dynamics and the residues, which form the related contacts called as folding nucleus residues (FNRs). In this work, the FNRs in proteins are identified by using quantities which characterize the topology of residue contact networks of proteins. By comparing the specificities of residues with the network quantities K(R), L(R), and D(R), up to 90% FNRs of six typical proteins found experimentally are identified. It is found that the FNRs behave the full-closeness centrals rather than degree or closeness centers in the residue contact network, implying that they are important to the folding cooperativity of proteins. Our study shows that the FNRs can be identified solely from the native structures of proteins based on the analysis of residue contact network without any knowledge of the transition state ensemble.
authors.affiliation: National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing 210093, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D012680:Sensitivity and Specificity; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins