title: Relationship between local structural entropy and protein thermostability.
abstract: We developed a technique to compute structural entropy directly from protein sequences. We explored the possibility of using structural entropy to identify residues involved in thermal stabilization of various protein families. Examples include methanococcal adenylate kinase, Ribonuclease HI and holocytochrome c(551). Our results show that the positions of the largest structural entropy differences between wild type and mutant usually coincide with the residues relevant to thermostability. We also observed a good linear relationship between the average structural entropy and the melting temperatures for adenylate kinase and its chimeric constructs. To validate this linear relationship, we compiled a large dataset comprised of 1153 sequences and found that most protein families still display similar linear relationships. Our results suggest that the multitude of interactions involved in thermal stabilization may be generalized into the tendency of proteins to maintain local structural conservation. The linear relationship between structural entropy and protein thermostability should be useful in the study of protein thermal stabilization.
authors.affiliation: Department of Life Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chen-Hsiung
authors.initials: CH
authors.lastname: Chan
authors.forename: Han-Kuen
authors.initials: HK
authors.lastname: Liang
authors.forename: Nai-Wan
authors.initials: NW
authors.lastname: Hsiao
authors.forename: Ming-Tat
authors.initials: MT
authors.lastname: Ko
authors.forename: Ping-Chiang
authors.initials: PC
authors.lastname: Lyu
authors.forename: Jenn-Kang
authors.initials: JK
authors.lastname: Hwang
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D003574:Cytochrome c Group / Q000737:chemistry; D019277:Entropy; D004795:Enzyme Stability; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000032:analysis / Q000737:chemistry*; D016914:Ribonuclease H / Q000737:chemistry; D044366:Transition Temperature
chemical_list: D001426:Bacterial Proteins; D003574:Cytochrome c Group; D011506:Proteins; C017167:cytochrome C(551); D000263:Adenylate Kinase; D016914:Ribonuclease H; C078856:ribonuclease HI