%0 Journal Article %1 ISI:000239829500006 %A Mitomo, Daisuke %A Nakamura, Hironori K. %A Ikeda, Kazuyoshi %A Yamagishi, Akihiko %A Higo, Junichi %C DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA %D 2006 %I WILEY-LISS %J PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS %K PCA Phi-values SH3 analysis atom barrier charge domain free-energy neutralization %N 4 %P 883-894 %R 10.1002/prot.21069 %T Transition state of a SH3 domain detected with principle component analysis and a charge-neutralized all-atom protein model %V 64 %X The src SH3 domain has been known to be a two-state folder near room temperature. However, in a previous study with an all-atom model simulation near room temperature, the transition state of this protein was not successfully detected on a free-energy profile using two axes: the radius of gyration (R-g) and native contact reproduction ratio (Q value). In this study, we focused on an atom packing effect to characterize the transition state and tried another analysis to detect it. To explore the atom packing effect more efficiently, we introduced a charge-neutralized all-atom model, where all of the atoms in the protein and water molecules were treated explicitly, but their partial atomic charges were set to zero. Ten molecular dynamics simulations were performed starting from the native structure at 300 K, where the simulation length of each run was 90 ns, and the protein unfolded in all runs. The integrated trajectories (10 X 90 = 900 ns) were analyzed by a principal component analysis (PCA) and showed a clear free-energy barrier between folded- and unfolded-state conformational clusters in a conformational space generated by PICA. There were segments that largely deformed when the conformation passed through the free-energy barrier. These segments correlated well with the structural core regions characterized by large phi-values, and the atom-packing changes correlated with the conformational deformations. Interestingly, using the same simulation data, no significant barrier was found in a free-energy profile using the R-g and Q values for the coordinate axes. These results suggest that the atom packing effect may be one of the most important determinants of the transition state.

@article{ISI:000239829500006, abstract = {{The src SH3 domain has been known to be a two-state folder near room temperature. However, in a previous study with an all-atom model simulation near room temperature, the transition state of this protein was not successfully detected on a free-energy profile using two axes: the radius of gyration (R-g) and native contact reproduction ratio (Q value). In this study, we focused on an atom packing effect to characterize the transition state and tried another analysis to detect it. To explore the atom packing effect more efficiently, we introduced a charge-neutralized all-atom model, where all of the atoms in the protein and water molecules were treated explicitly, but their partial atomic charges were set to zero. Ten molecular dynamics simulations were performed starting from the native structure at 300 K, where the simulation length of each run was 90 ns, and the protein unfolded in all runs. The integrated trajectories (10 X 90 = 900 ns) were analyzed by a principal component analysis (PCA) and showed a clear free-energy barrier between folded- and unfolded-state conformational clusters in a conformational space generated by PICA. There were segments that largely deformed when the conformation passed through the free-energy barrier. These segments correlated well with the structural core regions characterized by large phi-values, and the atom-packing changes correlated with the conformational deformations. Interestingly, using the same simulation data, no significant barrier was found in a free-energy profile using the R-g and Q values for the coordinate axes. These results suggest that the atom packing effect may be one of the most important determinants of the transition state.}}, added-at = {2009-01-12T06:27:08.000+0100}, address = {{DIV JOHN WILEY \& SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA}}, affiliation = {{Higo, J (Reprint Author), Tokyo Univ Pharm \& Life Sci, Sch Life Sci, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. Tokyo Univ Pharm \& Life Sci, Sch Life Sci, Hachioji, Tokyo 1920392, Japan. Gifu Univ, Ctr Emerging Infect Dis, Div Prion Res, Gifu, Japan. Natl Inst Adv Ind Sci \& Technol, Computat Biol Res Ctr, Tokyo, Japan.}}, author = {Mitomo, Daisuke and Nakamura, Hironori K. and Ikeda, Kazuyoshi and Yamagishi, Akihiko and Higo, Junichi}, author-email = {{higo@ls.toyaku.ac.jp}}, biburl = {https://www.bibsonomy.org/bibtex/26739615280baa57a2e827d41b6cab05d/huiyangsfsu}, cited-references = {{ALM E, 1999, CURR OPIN STRUC BIOL, V9, P189. ALM E, 1999, P NATL ACAD SCI USA, V96, P11305. ALONSO DOV, 1998, PROTEIN SCI, V7, P860. AMADEI A, 1993, PROTEINS, V17, P412. BOND CJ, 1997, P NATL ACAD SCI USA, V94, P13409. BRYNGELSON JD, 1995, PROTEINS, V21, P17. CHEUNG MS, 2002, P NATL ACAD SCI USA, V99, P685. CHO SS, 2006, P NATL ACAD SCI USA, V103, P586, DOI 10.1073/pnas.0509768103. CLEMENTI C, 2000, J MOL BIOL, V298, P937. COBOS ES, 2003, J MOL BIOL, V328, P221, DOI 10.1016/S0022-2836(03)00273-0. EVANS DJ, 1983, PHYS LETT A, V98, P433. FERNANDEZESCAMILLA AM, 2004, P NATL ACAD SCI USA, V101, P2834, DOI 10.1073/pnas.0304180101. FERSHT A, 1999, STRUCTURE MECH PROTE, P540. FERSHT AR, 1995, CURR OPIN STRUC BIOL, V5, P79. GALZITSKAYA OV, 1999, P NATL ACAD SCI USA, V96, P11229. GO N, 1983, ANNU REV BIOPHYS BIO, V12, P183. GRANTCHAROVA V, 2001, CURR OPIN STRUC BIOL, V11, P70. GRANTCHAROVA VP, 1997, BIOCHEMISTRY-US, V36, P15685. GRANTCHAROVA VP, 1998, NAT STRUCT BIOL, V5, P714. GRANTCHAROVA VP, 2001, J MOL BIOL, V306, P555. GSPONER J, 2001, J MOL BIOL, V309, P285. GSPONER J, 2002, P NATL ACAD SCI USA, V99, P6719. GUIJARRO JI, 1998, J MOL BIOL, V276, P657. GUO WH, 2004, PROTEINS, V55, P395, DOI 10.1002/prot.20053. HIGO J, 1997, PROTEIN ENG, V10, P373. HUBNER IA, 2005, J MOL BIOL, V349, P424, DOI 10.1016/j.jmb.2005.03.050. JACKSON SE, 1991, BIOCHEMISTRY-US, V30, P10428. JORGENSEN WL, 1983, J CHEM PHYS, V79, P926. KAMIYA N, 2002, PROTEIN SCI, V11, P2297, DOI 10.1110/ps.0213102. KIM DE, 2000, J MOL BIOL, V298, P971. KITAO A, 1991, CHEM PHYS, V158, P447. KOGA N, 2001, J MOL BIOL, V313, P171. KOLLMAN PA, 1997, COMPUTER SIMULATION, P83. LARSON SM, 2003, J MOL BIOL, V332, P275, DOI 10.1016/S0022-2836(03)00832-5. LI AJ, 1994, P NATL ACAD SCI USA, V91, P10430. LI AJ, 1996, J MOL BIOL, V257, P412. LINDORFFLARSEN K, 2003, BIOPHYS J, V85, P1207. LINDORFFLARSEN K, 2004, NAT STRUCT MOL BIOL, V11, P443, DOI 10.1038/nsmb765. MARTINEZ JC, 1999, NAT STRUCT BIOL, V6, P1010. MAXWELL KL, 2005, PROTEIN SCI, V14, P602, DOI 10.1110/ps.041205405. MCCALLISTER EL, 2000, NAT STRUCT BIOL, V7, P669. MORIKAMI K, 1992, COMPUT CHEM, V16, P243. MUNOZ V, 1999, P NATL ACAD SCI USA, V96, P11311. NAKAJIMA N, 1997, J PHYS CHEM B, V101, P817. NAKAMURA HK, 2004, CHEM PHYS, V307, P259, DOI 10.1016/j.chemphys.2004.07.011. NAKAMURA HK, 2004, PROTEINS, V55, P99. ONUCHIC JN, 1997, ANNU REV PHYS CHEM, V48, P545. PLAXCO KW, 1998, BIOCHEMISTRY-US, V37, P2529. PLAXCO KW, 2000, BIOCHEMISTRY-US, V39, P11177. RIDDLE DS, 1999, NAT STRUCT BIOL, V6, P1016. RYCKAERT JP, 1977, J COMPUT PHYS, V23, P327. SHEA JE, 2001, ANNU REV PHYS CHEM, V52, P499. SHEA JE, 2002, P NATL ACAD SCI USA, V99, P16064, DOI 10.1073/pnas.242293099. TEETER MM, 1990, J PHYS CHEM-US, V94, P8091. TERNSTROM T, 1999, P NATL ACAD SCI USA, V96, P14854. TSAI J, 1999, J MOL BIOL, V291, P215. WOLYNES PG, 1995, SCIENCE, V267, P1619. XU WQ, 1997, NATURE, V385, P595. ZARRINEAFSAR A, 2004, METHODS, V34, P41, DOI 10.1016/j.ymeth.2004.03.013.}}, doc-delivery-number = {{074RM}}, doi = {{10.1002/prot.21069}}, interhash = {fb8ad81309d5023cde0f1473fd747ad0}, intrahash = {6739615280baa57a2e827d41b6cab05d}, issn = {{0887-3585}}, journal = {{PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS}}, journal-iso = {{Proteins}}, keywords = {PCA Phi-values SH3 analysis atom barrier charge domain free-energy neutralization}, keywords-plus = {{MOLECULAR-DYNAMICS SIMULATIONS; SQUEEZED EXPONENTIAL KINETICS; FREE-ENERGY LANDSCAPE; FOLDING KINETICS; CHYMOTRYPSIN INHIBITOR-2; HYDROPHOBIC CORE; NATIVE TOPOLOGY; SRC; WATER; ENSEMBLE}}, language = {{English}}, month = {{SEP 1}}, note = {Transition state of a SH3 domain detected with principle component analysis and a charge-neutralized all-atom protein model (p 883-894) Daisuke Mitomo, Hironori K. Nakamura, Kazuyoshi Ikeda, Akihiko Yamagishi, Junichi Higo Published Online: Jun 28 2006 4:14PM DOI: 10.1002/prot.21069 }, number = {{4}}, number-of-cited-references = {{59}}, pages = {{883-894}}, publisher = {{WILEY-LISS}}, subject-category = {{Biochemistry \& Molecular Biology; Biophysics}}, times-cited = {{1}}, timestamp = {2009-01-12T06:27:08.000+0100}, title = {{Transition state of a SH3 domain detected with principle component analysis and a charge-neutralized all-atom protein model}}, type = {{Article}}, unique-id = {{ISI:000239829500006}}, volume = {{64}}, year = {{2006}} }