Statistical properties and kinetics of end-end contact formation of unfolded polypeptides: A systematic molecular dynamics study

Ping, Guanghui; Dastidar, Shubhra Ghosh; Duan, Yong

doi:10.1063/1.2430712

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…8͒ in explicit water, and have compared the results to normal molecular dynamics and aMDt simulations. The end-to-end contact formation rate for this and similar systems has been studied by tryptophan triplet quenching, 19,20 fluorescence resonance energy transfer 21 FRET and molecular dynamics simulations, [22][23][24] and the contact time is estimated to be in the nanosecond timescale.…”

Section: Peptide Loop-closure Dynamics and Convergencementioning

confidence: 99%

Sampling of slow diffusive conformational transitions with accelerated molecular dynamics

Hamelberg

Oliveira

McCammon

2007

The Journal of Chemical Physics

226

299

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Slow diffusive conformational transitions play key functional roles in biomolecular systems. Our ability to sample these motions with molecular dynamics simulation in explicit solvent is limited by the slow diffusion of the solvent molecules around the biomolecules. Previously, we proposed an accelerated molecular dynamics method that has been shown to efficiently sample the torsional degrees of freedom of biomolecules beyond the millisecond timescale. However, in our previous approach, large-amplitude displacements of biomolecules are still slowed by the diffusion of the solvent. Here we present a unified approach of efficiently sampling both the torsional degrees of freedom and the diffusive motions concurrently. We show that this approach samples the configuration space more efficiently than normal molecular dynamics and that ensemble averages converge faster to the correct values.

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Section: Peptide Loop-closure Dynamics and Convergencementioning

confidence: 99%

Sampling of slow diffusive conformational transitions with accelerated molecular dynamics

Hamelberg

Oliveira

McCammon

2007

The Journal of Chemical Physics

226

299

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“…In particular, disordered peptides having the sequence C(AGQ) j W (j ¼ 1-9) have been extensively characterized by means of tryptophan triplet quenching by cysteine, finding that the loop formation probability in aqueous buffer scales with chain length similarly to a flexible chain with a small amount of excluded volume. Because of the richness of experimental data available, the AGQ repeat has been used as a benchmark for unstructured polypeptides in various works (29)(30)(31)(32). However, the peculiarity of the sequence, in particular the high content of glycines and the absence of charged residues, strongly limits the comparison with the heterogeneous naturally disordered sequences.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Contact Formation and End-to-End Distance Distributions of Swollen Disordered Peptides

Soranno

Longhi

Bellini

et al. 2009

Biophysical Journal

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Unstructured polypeptide chains are subject to various degrees of swelling or compaction depending on the combination of solvent condition and amino acid sequence. Highly denatured proteins generally behave like random-coils with excluded volume repulsion, whereas in aqueous buffer more compact conformations have been observed for the low-populated unfolded state of globular proteins as well as for naturally disordered sequences. To quantitatively account for the different mechanisms inducing the swelling of polypeptides, we have examined three 14-residues peptides in aqueous buffer and in denaturant solutions, including the well characterized AGQ repeat as a reference and two variants, in which we have successively introduced charged side chains and removed the glycines. Quenching of the triplet state of tryptophan by close contact with cysteine has been used in conjunction with Förster resonance energy transfer to study the equilibrium and kinetic properties of the peptide chains. The experiments enable accessing end-to-end root mean-square distance, probability of end-to-end contact formation and intrachain diffusion coefficient. The data can be coherently interpreted on the basis of a simple chain model with backbone angles obtained from a library of coil segments of proteins and hard sphere repulsion at each Calpha position. In buffered water, we find that introducing charges in a glycine-rich sequence induces a mild chain swelling and a significant speed-up of the intrachain dynamics, whereas the removal of the glycines results in almost a two-fold increase of the chain volume and a drastic slowing down. In denaturants we observe a pronounced swelling of all the chains, with significant differences between the effect of urea and guanidinium chloride.

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“…25,[27][28][29][30][31][32][33][34][35][36] The end-to-end contact formation dynamics of the penta-peptide Cys-Ala-Gly-Gln-Trp (CAGQW) has been experimentally studied with triplet quenching. 22 The time scale of the end-to-end contact formation of this peptide was determined to be on the order of 100 ns, a time-scale which is accessible in atomically detailed MD simulations.…”

Section: Introductionmentioning

confidence: 99%

“…The end-to-end contact formation of amino acid residues is one of the elementary processes in protein folding and has been extensively studied both experimentally − and theoretically. ,− The end-to-end contact formation dynamics of the penta-peptide Cys-Ala-Gly-Gln-Trp (CAGQW) has been experimentally studied with triplet quenching . The time scale of the end-to-end contact formation of this peptide was determined to be on the order of 100 ns, a time-scale which is accessible in atomically detailed MD simulations.…”

Section: Introductionmentioning

confidence: 99%

Structure and Dynamics of End-to-End Loop Formation of the Penta-Peptide Cys-Ala-Gly-Gln-Trp in Implicit Solvents

Yeh

Wallqvist

2009

J. Phys. Chem. B

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To investigate the effects of implicit solvents on peptide structure and dynamics, we performed extensive molecular dynamics simulations on the penta-peptide Cys-Ala-Gly-Gln-Trp. Two different implicit solvent models based on the CHARMM22 all-atom force field were used. Structural properties of the peptide such as distributions of end-to-end distances and dihedral angles obtained from molecular dynamics simulations with implicit solvent models were in a good agreement with those obtained from a previous explicit solvent simulation using the same force field. Representative structures observed in explicit solvent were sampled by implicit solvent models but with different relative probabilities. However, we observed significant differences in dynamical properties in explicit and implicit solvent models when we used traditional methods for the temperature control, such as Nosé-Hoover or Berendsen thermostats. The explicitly solvated peptide displayed the slowest dynamics in both end-to-end contact formation and intrinsic diffusive motion of end-to-end distances. A closer agreement between implicit and explicit solvated peptide dynamics was observed when Langevin dynamics with a friction coefficient of 10 ps -1 was used to maintain the temperature of the systems.

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Statistical properties and kinetics of end-end contact formation of unfolded polypeptides: A systematic molecular dynamics study

Cited by 5 publications

References 30 publications

Sampling of slow diffusive conformational transitions with accelerated molecular dynamics

Sampling of slow diffusive conformational transitions with accelerated molecular dynamics

Kinetics of Contact Formation and End-to-End Distance Distributions of Swollen Disordered Peptides

Structure and Dynamics of End-to-End Loop Formation of the Penta-Peptide Cys-Ala-Gly-Gln-Trp in Implicit Solvents

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