Observation of multiple folding pathways of <i>β</i>-hairpin trpzip2 from independent continuous folding trajectories

Chen, Changjun; Xiao, Yi

doi:10.1093/bioinformatics/btn029

Cited by 36 publications

(29 citation statements)

References 48 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation confirms our MD simulation in previous works. 45,50,51 Figure 2. Graphic representation for three typical helices: p-helix, a-helix, and 3 10 -helix, and two alternative transition processes from a-helix to p-helix.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, many other works presented the multifolding pathways of trpzip2, [41][42][43][44] and this was also confirmed by our recent work with direct MD simulations. 45 Through free energy analysis on the data from 38 100-ns trajectories, we obtained six meta-stable states, named from M1 to M6. In this article, we will calculate the free energy differences between these meta-stable states and native state and compare them with the results from MD simulations.…”

Section: Modelsmentioning

confidence: 99%

See 1 more Smart Citation

Accurate free energy calculation along optimized paths

Chen

Xiao

2009

J Comput Chem

View full text Add to dashboard Cite

The path-based methods of free energy calculation, such as thermodynamic integration and free energy perturbation, are simple in theory, but difficult in practice because in most cases smooth paths do not exist, especially for large molecules. In this article, we present a novel method to build the transition path of a peptide. We use harmonic potentials to restrain its nonhydrogen atom dihedrals in the initial state and set the equilibrium angles of the potentials as those in the final state. Through a series of steps of geometrical optimization, we can construct a smooth and short path from the initial state to the final state. This path can be used to calculate free energy difference. To validate this method, we apply it to a small 10-ALA peptide and find that the calculated free energy changes in helix-helix and helix-hairpin transitions are both self-convergent and cross-convergent. We also calculate the free energy differences between different stable states of beta-hairpin trpzip2, and the results show that this method is more efficient than the conventional molecular dynamics method in accurate free energy calculation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Modelsmentioning

confidence: 99%

Accurate free energy calculation along optimized paths

Chen

Xiao

2009

J Comput Chem

View full text Add to dashboard Cite

show abstract

“…41 All the simulations are carried out at 298 K. The time step is 1 fs. The initial structure is an extended b-strand.…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

“…41 However, Table 1 shows that these two states have the similar values of the RMSD, R g , and probability distribution of hydrogen bonds, i.e., these two states should be considered as a single state. The MCL algorithm indeed groups them into one cluster C1.…”

Section: Comparing Basins Detected By MCL Algorithm and By Conventionmentioning

confidence: 99%

Improvements of network approach for analysis of the folding free‐energy surface of peptides and proteins

2010

View full text Add to dashboard Cite

Folding network is an effective approach to investigate the high-dimensional free-energy surface of peptide and protein folding, and it can avoid the limitations of the projected free-energy surface based on two-order parameters. In this article, we present improvements of the effectiveness and accuracy of the folding network analysis based on Markov cluster (MCL) algorithm. We used this approach to investigate the folding free-energy surface of the beta-hairpin peptide trpzip2 and found the folding network is able to determine the basins and folding paths of trpzip2 more clearly and accurately than the two-dimensional free-energy surface.

show abstract

“…Among the latter, several have demonstrated stability and folding of trpzip models using OPLS-AA, 4, 10 AMBER ff96, [11][12][13][14][15] and AMBER ff99SB (Ref. 16) all-atom molecular mechanics force fields.…”

Section: Introductionmentioning

confidence: 99%

Evaluating force field accuracy with long-time simulations of a β-hairpin tryptophan zipper peptide

Hayre¹,

Singh²,

Cox³

2011

The Journal of Chemical Physics

View full text Add to dashboard Cite

We have combined graphics processing unit-accelerated all-atom molecular dynamics with parallel tempering to explore the folding properties of small peptides in implicit solvent on the time scale of microseconds. We applied this methodology to the synthetic β-hairpin, trpzip2, and one of its sequence variants, W2W9. Each simulation consisted of over 8 μs of aggregated virtual time. Several measures of folding behavior showed good convergence, allowing comparison with experimental equilibrium properties. Our simulations suggest that the intramolecular interactions of tryptophan side chains are responsible for much of the stability of the native fold. We conclude that the ff99 force field combined with ff96 φ and ψ dihedral energies and an implicit solvent can reproduce plausible folding behavior in both trpzip2 and W2W9.

show abstract

Observation of multiple folding pathways of β-hairpin trpzip2 from independent continuous folding trajectories

Cited by 36 publications

References 48 publications

Accurate free energy calculation along optimized paths

Accurate free energy calculation along optimized paths

Improvements of network approach for analysis of the folding free‐energy surface of peptides and proteins

Evaluating force field accuracy with long-time simulations of a β-hairpin tryptophan zipper peptide

Contact Info

Product

Resources

About