Atomic Simulations of Protein Folding, Using the Replica Exchange Algorithm

Nymeyer, Hugh; Gnanakaran, S.; Garcı́a, Angel E.

doi:10.1016/s0076-6879(04)83006-4

Cited by 133 publications

(146 citation statements)

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“…as suggested by Nymeyer et al 20 on the basis of somewhat different arguments. If, in addition, the heat capacity is constant over the entire interval, Eq.…”

Section: Formal Developmentsmentioning

confidence: 91%

A constant entropy increase model for the selection of parallel tempering ensembles

Sabo

Meuwly

Freeman

et al. 2008

The Journal of Chemical Physics

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The present paper explores a simple approach to the question of parallel tempering temperature selection. We argue that to optimize the performance of parallel tempering it is reasonable to require that the increase in entropy between successive temperatures be uniform over the entire ensemble. An estimate of the system's heat capacity, obtained either from experiment, a preliminary simulation, or a suitable physical model, thus provides a means for generating the desired tempering ensemble. Applications to the two-dimensional Ising problem indicate that the resulting method is effective, simple to implement, and robust with respect to its sensitivity to the quality of the underlying heat capacity model.

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“…as suggested by Nymeyer et al 20 on the basis of somewhat different arguments. If, in addition, the heat capacity is constant over the entire interval, Eq.…”

Section: Formal Developmentsmentioning

confidence: 91%

A constant entropy increase model for the selection of parallel tempering ensembles

Sabo

Meuwly

Freeman

et al. 2008

The Journal of Chemical Physics

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“…In atomic-level RE simulations, temperature-exchange attempts usually are made periodically in time, i.e., the MC or MD evolution is interrupted, temperature swap proposal(s) are made, and the proposals are either accepted or rejected (4,6). In keeping with the continuous-time nature of our network model, we simulate the effect of temperature exchanges by introducing an additional rate parameter ␣, which controls the overall scaling of the temperature-exchange rate relative to the folding and unfolding rates.…”

Section: Theorymentioning

confidence: 99%

“…Periodically, coordinates are exchanged by using a Metropolis criterion (3) that ensures that at any given temperature a canonical distribution is realized. RE methods, particularly REMD (4), have become very popular for the study of protein biophysics, including peptide and protein folding (5,6), aggregation (7)(8)(9), and protein-ligand interactions (10,11). Previous studies of protein folding appear to show a significant increase in the number of reversible folding events in REMD simulations versus conventional MD (12,13).…”

mentioning

confidence: 99%

Simulating replica exchange simulations of protein folding with a kinetic network model

Zheng

Andrec

Gallicchio

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

149

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Replica exchange (RE) is a generalized ensemble simulation method for accelerating the exploration of free-energy landscapes, which define many challenging problems in computational biophysics, including protein folding and binding. Although temperature RE (T-RE) is a parallel simulation technique whose implementation is relatively straightforward, kinetics and the approach to equilibrium in the T-RE ensemble are very complicated; there is much to learn about how to best employ T-RE to protein folding and binding problems. We have constructed a kinetic network model for RE studies of protein folding and used this reduced model to carry out ''simulations of simulations'' to analyze how the underlying temperature dependence of the conformational kinetics and the basic parameters of RE (e.g., the number of replicas, the RE rate, and the temperature spacing) all interact to affect the number of folding transitions observed. When protein folding follows anti-Arrhenius kinetics, we observe a speed limit for the number of folding transitions observed at the low temperature of interest, which depends on the maximum of the harmonic mean of the folding and unfolding transition rates at high temperature. The results shown here for the network RE model suggest ways to improve atomic-level RE simulations such as the use of ''training'' simulations to explore some aspects of the temperature dependence for folding of the atomic-level models before performing RE studies.anti-Arrhenius ͉ Markov process ͉ parallel tempering O ne of the key challenges in the computer simulation of proteins at the atomic level is the sampling of conformational space. The efficiency of many common sampling protocols, such as Monte Carlo (MC) and molecular dynamics (MD), is limited by the need to cross high free-energy barriers between conformational states and rugged energy landscapes. One class of methods for studying equilibrium properties of quasi-ergodic systems that has received a great deal of recent attention is based on the replica exchange (RE) algorithm (1, 2) (also known as parallel tempering). To accomplish barrier crossings, RE methods simulate a series of replicas over a range of temperatures. Periodically, coordinates are exchanged by using a Metropolis criterion (3) that ensures that at any given temperature a canonical distribution is realized. RE methods, particularly REMD (4), have become very popular for the study of protein biophysics, including peptide and protein folding (5, 6), aggregation (7-9), and protein-ligand interactions (10, 11). Previous studies of protein folding appear to show a significant increase in the number of reversible folding events in REMD simulations versus conventional MD (12,13). Given the wide use of REMD, a better understanding of the RE algorithm and how it can be used most effectively for the study of protein folding and binding is of considerable interest.The effectiveness of RE methods is determined by the number of temperatures (replicas) that are simulated, their range and spacing, the rate at ...

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“…Instead, we utilized the well-documented replica exchange methodology (35) to permit a thermodynamic "competition" between parallel and antiparallel assemblies. See Methods section for a brief discussion on why these populations should not be considered predictions on relative populations at 280 K; instead, the intention of the simulations was to identify sequences for which there is significant enrichment in antiparallel structures that are competitive in energy with parallel configurations.…”

Section: Replica Exchange (Rex) Simulationsmentioning

confidence: 99%

Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,

et al. 2006

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A detailed understanding of the mechanisms by which particular amino acid sequences can give rise to more than one folded structure, such as for proteins that undergo large conformational changes or misfolding, is a long-standing objective of protein chemistry. Here we describe the crystal structures of a single coiled-coil peptide in distinct parallel and antiparallel tetrameric configurations and further describe the parallel or antiparallel crystal structures of several related peptide sequences; the antiparallel tetrameric assemblies represents the first crystal structures of GCN4-derived peptides exhibiting such a configuration. Intriguingly, substitution of a single solvent-exposed residue enabled the parallel coiled-coil tetramer GCN4-pLI to populate the antiparallel configuration, suggesting that the two configurations are close enough in energy for subtle sequence changes to have important structural consequences. We present a structural analysis of the small changes to helix register and side chain conformations that accommodate the two configurations, and have supplemented these results using solution studies and a molecular dynamics energetic analysis using a replica exchange methodology. Considering the previous examples of structural nonspecificity in coiled-coil peptides, the findings reported here not only emphasize the predisposition of the coiled-coil motif to adopt multiple configurations, but also call attention to the associated risk that observed crytstal structures may not represent the only (or even the major) species present in solution.The diverse functional prowess of proteins derives in large part from their ability to adopt unique tertiary and quaternary structures, and a major goal of protein chemistry is thus to understand in detail how primary amino acid sequences specify three-dimensional structures. Conformational changes and protein misfolding are critical events in biological processes and diseases in which a given polypeptide sequence gives rise to more than one folded structure, but detailed structural analyses of such processes are often difficult because multiple † We thank the Skaggs Institute for Chemical Biology for financial support, and NSF for a predoctoral fellowship (L.J.L.). § Coordinates have been deposited in the RCSB Protein Data Bank: peptide 2, 1W5K; E20C (peptide 3), 2CCN; E20S (peptide 4), 2CCE, 2CCF; ABA-pLI (peptide 5), 1W5I; peptide 6, 1W5J; E20C Y17H (peptide 7), 1W5H; E20C Ak (peptide 8), 1W5G.* Address correspondence to this author. (858) 784-2700 (phone); (858) 784-2798 (fax); ghadiri@scripps.edu (e-mail).. ‡ These authors contributed equally to this study.Supporting Information Available. Additional figures, CD wavelength scans, thermal denaturation curves, crystallization statistics. This material is available free of charge via the Internet at http://pubs.acs.org. 1 Abbreviations: ABA, acetamidobenzoic acid; CD, circular dichroism; Cys, cysteine, Glu, glutamic acid; HPLC, high-performance liquid chromatography; Lys, lysine; MALDI-TOF, matr...

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Atomic Simulations of Protein Folding, Using the Replica Exchange Algorithm

Cited by 133 publications

References 50 publications

A constant entropy increase model for the selection of parallel tempering ensembles

A constant entropy increase model for the selection of parallel tempering ensembles

Simulating replica exchange simulations of protein folding with a kinetic network model

Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,

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Atomic Simulations of Protein Folding, Using the Replica Exchange Algorithm

Cited by 133 publications

References 50 publications

A constant entropy increase model for the selection of parallel tempering ensembles

A constant entropy increase model for the selection of parallel tempering ensembles

Simulating replica exchange simulations of protein folding with a kinetic network model

Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution,

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Coiled Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution^,