%0 Journal Article %1 ISI:000238315600056 %A van der Spoel, D %A Seibert, MM %C ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA %D 2006 %I AMERICAN PHYSICAL SOC %J PHYSICAL REVIEW LETTERS %K kinetics thermodynamics %N 23 %R 10.1103/PhysRevLett.96.238102 %T Protein folding kinetics and thermodynamics from atomistic simulations %V 96 %X Determining protein folding kinetics and thermodynamics from all-atom molecular dynamics (MD) simulations without using experimental data represents a formidable scientific challenge because simulations can easily get trapped in local minima on rough free energy landscapes. This necessitates the computation of multiple simulation trajectories, which can be independent from each other or coupled in some manner, as, for example, in the replica exchange MD method. Here we present results obtained with a new analysis tool that allows the deduction of faithful kinetics data from a heterogeneous ensemble of simulation trajectories. The method is demonstrated on the decapeptide Chignolin for which we predict folding and unfolding time constants of 1.0 +/- 0.3 and 2.6 +/- 0.4 mu s, respectively. We also derive the energetics of folding, and calculate a realistic melting curve for Chignolin.

@article{ISI:000238315600056, abstract = {{Determining protein folding kinetics and thermodynamics from all-atom molecular dynamics (MD) simulations without using experimental data represents a formidable scientific challenge because simulations can easily get trapped in local minima on rough free energy landscapes. This necessitates the computation of multiple simulation trajectories, which can be independent from each other or coupled in some manner, as, for example, in the replica exchange MD method. Here we present results obtained with a new analysis tool that allows the deduction of faithful kinetics data from a heterogeneous ensemble of simulation trajectories. The method is demonstrated on the decapeptide Chignolin for which we predict folding and unfolding time constants of 1.0 +/- 0.3 and 2.6 +/- 0.4 mu s, respectively. We also derive the energetics of folding, and calculate a realistic melting curve for Chignolin.}}, added-at = {2009-01-05T00:40:45.000+0100}, address = {{ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA}}, affiliation = {{van der Spoel, D (Reprint Author), Uppsala Univ, Biomed Ctr, Dept Cellular \& Mol Biol, Box 596, SE-75124 Uppsala, Sweden. Uppsala Univ, Biomed Ctr, Dept Cellular \& Mol Biol, SE-75124 Uppsala, Sweden.}}, article-number = {{238102}}, author = {van der Spoel, D and Seibert, MM}, author-email = {{spoel@xray.bmc.uu.se}}, biburl = {https://www.bibsonomy.org/bibtex/29269876f9d3071e7b55603f36f4ba31d/huiyangsfsu}, cited-references = {{BARRON LD, 1997, BIOCHEMISTRY-US, V36, P13143. BRADLEY P, 2005, SCIENCE, V309, P1868, DOI 10.1126/science.1113801. BUSSI G, 2006, PHYS REV LETT, V96, ARTN 090601. DAIDONE I, 2005, J AM CHEM SOC, V127, P14825, DOI 10.1021/ja0533383f. DU DG, 2004, P NATL ACAD SCI USA, V101, P15915, DOI 10.1073/pnas.0405904101. ESSMANN U, 1995, J CHEM PHYS, V103, P8577. HONDA S, 2004, STRUCTURE, V12, P1507. HUKUSHIMA K, 1996, J PHYS SOC JPN, V65, P1604. JORGENSEN WL, 1983, J CHEM PHYS, V79, P926. JORGENSEN WL, 1996, J AM CHEM SOC, V118, P11225. KUMAR S, 1992, J COMPUT CHEM, V13, P1011. LAIO A, 2002, P NATL ACAD SCI USA, V99, P12562, DOI 10.1073/pnas.202427399. LINDAHL E, 2001, J MOL MODEL, V7, P306. LUZAR A, 1996, NATURE, V379, P55. MUNOZ V, 1997, NATURE, V390, P196. NELDER JA, 1965, COMPUT J, V7, P308. OKABE T, 2001, CHEM PHYS LETT, V335, P435. OKAMOTO Y, 2004, J MOL GRAPH MODEL, V22, P425, DOI 10.1016/j.jmgm.2003.12.009. PASCHEK D, 2004, PHYS REV LETT, V93, ARTN 238105. PITERA JW, 2003, P NATL ACAD SCI USA, V100, P7587, DOI 10.1073/pnas.1330954100. RAO F, 2003, J CHEM PHYS, V119, P4035, DOI 10.1063/1.1591721. RHEE YM, 2004, P NATL ACAD SCI USA, V101, P6456, DOI 10.1073/pnas.0307898101. SCHUELERFURMAN O, 2005, SCIENCE, V310, P638, DOI 10.1126/science.1112160. SEIBERT MM, 2005, J MOL BIOL, V354, P173, DOI 10.1016/j.jmb.2005.098.030. SHIRTS MR, 2001, PHYS REV LETT, V86, P4983. VANDERSPOEL D, 2003, J PHYS CHEM B, V107, P11178, DOI 10.1021/jp034108n. VANDERSPOEL D, 2005, J COMPUT CHEM, V26, P1701, DOI 10.1002/jcc.20291. VANDERSPOEL D, 2006, J CHEM THEORY COMPUT, V2, P1, DOI 10.1021/ct0502256. VANDERSPOEL D, 2006, J PHYS CHEM B, V110, P4393, DOI 10.1021/jp0572535. XU F, 1999, P NATL ACAD SCI USA, V96, P9057. XU Y, 2003, J AM CHEM SOC, V125, P15388, DOI 10.1021/ja037053b. ZHANG W, 2005, J CHEM PHYS, V123, ARTN 154105. ZHOU RH, 2001, P NATL ACAD SCI USA, V98, P14931. ZHOU RH, 2003, P NATL ACAD SCI USA, V100, P13280, DOI 10.1073/pnas.2233312100.}}, doc-delivery-number = {{053OX}}, doi = {{10.1103/PhysRevLett.96.238102}}, interhash = {a6d593e174bb64ba54e2b1e3ecff6f3d}, intrahash = {9269876f9d3071e7b55603f36f4ba31d}, issn = {{0031-9007}}, journal = {{PHYSICAL REVIEW LETTERS}}, journal-iso = {{Phys. Rev. Lett.}}, keywords = {kinetics thermodynamics}, keywords-plus = {{MOLECULAR-DYNAMICS SIMULATIONS; FREE-ENERGY LANDSCAPE; MONTE-CARLO METHOD; BETA-HAIRPIN; LIQUID WATER; STRUCTURE PREDICTION; EXPLICIT WATER; TRP-CAGE; MECHANISM; ENSEMBLE}}, language = {{English}}, month = {{JUN 16}}, number = {{23}}, number-of-cited-references = {{34}}, publisher = {{AMERICAN PHYSICAL SOC}}, subject-category = {{Physics, Multidisciplinary}}, times-cited = {{12}}, timestamp = {2009-01-05T00:40:45.000+0100}, title = {{Protein folding kinetics and thermodynamics from atomistic simulations}}, type = {{Article}}, unique-id = {{ISI:000238315600056}}, volume = {{96}}, year = {{2006}} }