%0 Journal Article %1 ISI:000258358100005 %A Monticelli, Luca %A Sorin, Eric J. %A Tieleman, D. Peter %A Pande, Vijay S. %A Colombo, Giorgio %C 111 RIVER ST, HOBOKEN, NJ 07030 USA %D 2008 %I JOHN WILEY & SONS INC %J JOURNAL OF COMPUTATIONAL CHEMISTRY %K computing distributed folding helix-coil protein transition %N 11 %P 1740-1752 %R 10.1002/jcc.20935 %T Molecular simulation of multistate peptide dynamics: A comparison between microsecond timescale sampling and multiple shorter trajectories %V 29 %X Molecular dynamics simulations of the RN24 peptide, which includes a diverse set of structurally heterogeneous states, are carried out in explicit solvent. Two approaches are employed and compared directly under identical simulation conditions. Specifically, we examine sampling by two individual long trajectories (microsecond timescale) and many shorter (MS) uncoupled trajectories. Statistical analysis of the structural properties indicates a qualitative agreement between these approaches. Microsecond timescale sampling gives large uncertainties on most structural metrics, while the shorter timescale of MS simulations results in slight structural memory for beta-structure starting states. Additionally, MS sampling detects numerous transitions on a relatively short timescale that are not observed in microsecond sampling, while long simulations allow for detection of a few transitions on significantly longer timescales. A correlation between the complex free energy landscape and the kinetics of the equilibrium is highlighted by principal component analysis on both simulation sets. This report highlights the increased precision of the MS approach when studying the kinetics of complex conformational change, while revealing the complementary insight and qualitative agreement offered by far fewer individual simulations on significantly longer timescales. (c) 2008 Wiley Periodicals, Inc.

@article{ISI:000258358100005, abstract = {{Molecular dynamics simulations of the RN24 peptide, which includes a diverse set of structurally heterogeneous states, are carried out in explicit solvent. Two approaches are employed and compared directly under identical simulation conditions. Specifically, we examine sampling by two individual long trajectories (microsecond timescale) and many shorter (MS) uncoupled trajectories. Statistical analysis of the structural properties indicates a qualitative agreement between these approaches. Microsecond timescale sampling gives large uncertainties on most structural metrics, while the shorter timescale of MS simulations results in slight structural memory for beta-structure starting states. Additionally, MS sampling detects numerous transitions on a relatively short timescale that are not observed in microsecond sampling, while long simulations allow for detection of a few transitions on significantly longer timescales. A correlation between the complex free energy landscape and the kinetics of the equilibrium is highlighted by principal component analysis on both simulation sets. This report highlights the increased precision of the MS approach when studying the kinetics of complex conformational change, while revealing the complementary insight and qualitative agreement offered by far fewer individual simulations on significantly longer timescales. (c) 2008 Wiley Periodicals, Inc.}}, added-at = {2009-01-11T01:34:12.000+0100}, address = {{111 RIVER ST, HOBOKEN, NJ 07030 USA}}, affiliation = {{Monticelli, L (Reprint Author), Helsinki Univ Technol, Phys Lab, Helsinki, Finland. {[}Monticelli, Luca; Tieleman, D. Peter] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada. {[}Monticelli, Luca; Colombo, Giorgio] Univ Milan, Ctr Biomol Interdisciplinary Studies \& Ind Applic, I-20131 Milan, Italy. {[}Sorin, Eric J.; Pande, Vijay S.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA. {[}Pande, Vijay S.] Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA. {[}Colombo, Giorgio] CNR, Ist Chim Riconoscimento Mol, I-20131 Milan, Italy.}}, author = {Monticelli, Luca and Sorin, Eric J. and Tieleman, D. Peter and Pande, Vijay S. and Colombo, Giorgio}, author-email = {{luca.monticelli@ucalgary.ca}}, biburl = {https://www.bibsonomy.org/bibtex/26efe85ba97fe135726c1d2f3b44b8611/huiyangsfsu}, cited-references = {{BERENDSEN HJC, 1984, J CHEM PHYS, V81, P3684. BERENDSEN HJC, 1995, COMPUT PHYS COMMUN, V91, P43. BIERZYNSKI A, 1982, P NATL ACAD SCI USA, V79, P2470. BROWN JE, 1971, BIOCHEM, V10, P470. CHODERA JD, 2007, J CHEM PHYS, V126, ARTN 155101. DARDEN T, 1993, J CHEM PHYS, V98, P10089. DAURA X, 1998, J COMPUT CHEM, V19, P535. DUAN Y, 1998, SCIENCE, V282, P740. EATON WA, 1998, ACCOUNTS CHEM RES, V31, P745. EATON WA, 2000, ANNU REV BIOPH BIOM, V29, P327. ESSMANN U, 1995, J CHEM PHYS, V103, P8577. FEENSTRA KA, 1999, J COMPUT CHEM, V20, P786. FEIG M, 2003, J PHYS CHEM B, V107, P2831, DOI 10.1021/jp027293y. FERSHT AR, 2002, P NATL ACAD SCI USA, V99, P14122. GARCIA AE, 2003, P NATL ACAD SCI USA, V100, P13898, DOI 10.1073/pnas.2335541100. HESS B, 1997, J COMPUT CHEM, V18, P1463. HESS B, 2002, J CHEM PHYS, V116, P209. KABSCH W, 1983, BIOPOLYMERS, V22, P2577. MIYAMOTO S, 1992, J COMPUT CHEM, V13, P952. MONTICELLI L, 2005, J PHYS CHEM B, V109, P20064, DOI 10.1021/jp054729b. NOE F, 2007, J CHEM PHYS, V126, ARTN 155102. OHKUBO YZ, 2003, P NATL ACAD SCI USA, V100, P13916, DOI 10.1073/pnas.2334257100. OSTERHOUT JJ, 1989, BIOCHEMISTRY-US, V28, P7059. PACI E, 2003, P NATL ACAD SCI USA, V100, P8217, DOI 10.1073/pnas.1331838100. PANDE VS, 2003, BIOPOLYMERS, V68, P91, DOI 10.1002/bip.10219. PARK S, 2006, J CHEM PHYS, V124, ARTN 054118. RHEE YM, 2004, P NATL ACAD SCI USA, V101, P6456, DOI 10.1073/pnas.0307898101. SCHAEFER M, 1998, J MOL BIOL, V284, P835. SCHAEFER M, 1999, THEOR CHEM ACC, V101, P194. SHIRTS M, 2000, SCIENCE, V290, P1903. SHOEMAKER KR, 1987, NATURE, V326, P563. SINGHAL N, 2004, J CHEM PHYS, V121, P415, DOI 10.1063/1.1738647. SINGHAL N, 2007, J CHEM PHYS, V126, UNSP 244101. SNOW CD, 2002, NATURE, V420, P102, DOI 10.1038/nature01160. SORIN EJ, 2003, BIOPHYS J, V85, P790. SORIN EJ, 2005, BIOPHYS J, V88, P2472. SORIN EJ, 2005, BIOPHYS J, V88, P2516. SORIN EJ, 2005, J COMPUT CHEM, V26, P682, DOI 10.1002/jcc.020208. SUGITA Y, 1999, CHEM PHYS LETT, V314, P141. SWOPE WC, 2004, J PHYS CHEM B, V108, P6571, DOI 10.1021/jp037421y. TIRADORIVES J, 1991, BIOCHEMISTRY-US, V30, P3864. ZAGROVIC B, 2001, J MOL BIOL, V313, P151. ZAGROVIC B, 2002, BIOPHYS J 2, V82, A474. ZAGROVIC B, 2002, J MOL BIOL, V324, P1051, DOI 10.1016/S0022-2836(02)01244-5.}}, doc-delivery-number = {{336IS}}, doi = {{10.1002/jcc.20935}}, interhash = {b73df4cca85e073cfd523bd7bed42820}, intrahash = {6efe85ba97fe135726c1d2f3b44b8611}, issn = {{0192-8651}}, journal = {{JOURNAL OF COMPUTATIONAL CHEMISTRY}}, journal-iso = {{J. Comput. Chem.}}, keywords = {computing distributed folding helix-coil protein transition}, keywords-plus = {{HELIX-COIL TRANSITION; PARTICLE MESH EWALD; SOLUTION CONFORMATIONS; BETA-HAIRPIN; FORCE-FIELD; C-PEPTIDE; STRUCTURED PEPTIDES; FOLDING SIMULATIONS; RIBONUCLEASE-A; ALPHA-HELICES}}, language = {{English}}, month = {{AUG}}, number = {{11}}, number-of-cited-references = {{44}}, pages = {{1740-1752}}, publisher = {{JOHN WILEY \& SONS INC}}, subject-category = {{Chemistry, Multidisciplinary}}, times-cited = {{0}}, timestamp = {2009-01-11T01:34:12.000+0100}, title = {{Molecular simulation of multistate peptide dynamics: A comparison between microsecond timescale sampling and multiple shorter trajectories}}, type = {{Article}}, unique-id = {{ISI:000258358100005}}, volume = {{29}}, year = {{2008}} }