Fluctuation power spectra reveal dynamical heterogeneity of peptides

Khatri, Bhavin S.; Yew, Zu Thur; Krivov, Sergei V.; McLeish, Tom; Paci, Emanuele

doi:10.1063/1.3456552

Cited by 4 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study proposed that the deviation could only be explained by a switch between parallel unfolding pathways and suggested that mechanical unfolding kinetics needs to account for the multidimensionality of the free-energy landscapes of proteins, which are crucial for understanding the behavior of proteins under the small forces experienced in vivo. In another study, the choice of the one-dimensional reaction coordinate probed in SMFS has been questioned due to the multidimensionality of protein energy landscapes [122]. It has been suggested that more information could be obtained about the multidimensional energy landscape from analysing the dynamical fluctuations of proteins using simulations and single molecule techniques [122].…”

Section: Associated Formula Refsmentioning

confidence: 99%

“…In another study, the choice of the one-dimensional reaction coordinate probed in SMFS has been questioned due to the multidimensionality of protein energy landscapes [122]. It has been suggested that more information could be obtained about the multidimensional energy landscape from analysing the dynamical fluctuations of proteins using simulations and single molecule techniques [122]. Figure 17: Recent development of a high speed AFM for SMFS force spectroscopy (A) The high speed AFM setup.…”

Section: Associated Formula Refsmentioning

confidence: 99%

See 1 more Smart Citation

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

2016

View full text Add to dashboard Cite

One of the most exciting developments in the field of biological physics in recent years is the ability to manipulate single molecules and probe their properties and function. Since its emergence over two decades ago, single molecule force spectroscopy has become a powerful tool to explore the response of biological molecules, including proteins, DNA, RNA and their complexes, to the application of an applied force. The force versus extension response of molecules can provide valuable insight into its mechanical stability, as well as details of the underlying energy landscape. In this review we will introduce the technique of single molecule force spectroscopy using the atomic force microscope (AFM), with particular focus on its application to study proteins. We will review the models which have been developed and employed to extract information from single molecule force spectroscopy experiments. Finally, we will end with a discussion of future directions in this field.

show abstract

Section: Associated Formula Refsmentioning

confidence: 99%

Section: Associated Formula Refsmentioning

confidence: 99%

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

2016

View full text Add to dashboard Cite

show abstract

“…The effect of the force on the distribution can be then removed and simulations performed with different forces used simultaneously to obtain an accurate estimation of the potential of mean force for all end-to-end distances. Simulations with the application of a constant force could also provide the fluctuations of the end-to-end distance that are measurable and provide information on their viscoelastic properties and insight on the free-energy landscape of the system [50].…”

Section: Concluding Discussionmentioning

confidence: 99%

“…Of particular interest is the spectrum of the fluctuations of the end-toend distance and its dependence on the constant-force applied. Fluctuations of the end-to-end distance is a quantity that can be measured through atomic force spectroscopy [49], and that provides a dynamical fingerprint of the underlying free energy landscape of the polypeptide chain [50].…”

Section: Uses and Limitations Of The Constant-force Bias Approachmentioning

confidence: 99%

Effect of external pulling forces on the length distribution of peptides

Batchelor¹,

Gowdy²,

Paci³

2015

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

“…Using our modified CHARMM code 50 we performed BXD simulations for 5 small model peptides: (1) 10-alanine (10-ALA) previously simulated in Refs. 36, 37, and 51, (2) 10-glycine (10-GLY), 51 (3) a 20 amino acid peptide (20-AA) with the sequence THR-TRP-ILE-GLN-ASN-GLY-SER-THR-LYS-TRP-TYR-GLN-ASN-GLY-SER-THR-LYS-ILE-TYR-THR, (4) a 12 amino acid peptide (12-AA) which is simply the first 12 residues of the above 20-AA sequence, and (5) a 13 amino acid peptide (denoted as 13-AA), with the first 13 residues of a 20-AA peptide studied previously. 52 As in previous work, the CHARMM19 force-field 53 and a simple implicit solvation model 54 have been used.…”

Section: A Bxd Numerical Experimentsmentioning

confidence: 99%

Peptide kinetics from picoseconds to microseconds using boxed molecular dynamics: Power law rate coefficients in cyclisation reactions

Shalashilin

Beddard

Paci

et al. 2012

The Journal of Chemical Physics

View full text Add to dashboard Cite

Molecular dynamics (MD) methods are increasingly widespread, but simulation of rare events in complex molecular systems remains a challenge. We recently introduced the boxed molecular dynamics (BXD) method, which accelerates rare events, and simultaneously provides both kinetic and thermodynamic information. We illustrate how the BXD method may be used to obtain high-resolution kinetic data from explicit MD simulations, spanning picoseconds to microseconds. The method is applied to investigate the loop formation dynamics and kinetics of cyclisation for a range of polypeptides, and recovers a power law dependence of the instantaneous rate coefficient over six orders of magnitude in time, in good agreement with experimental observations. Analysis of our BXD results shows that this power law behaviour arises when there is a broad and nearly uniform spectrum of reaction rate coefficients. For the systems investigated in this work, where the free energy surfaces have relatively small barriers, the kinetics is very sensitive to the initial conditions: strongly non-equilibrium conditions give rise to power law kinetics, while equilibrium initial conditions result in a rate coefficient with only a weak dependence on time. These results suggest that BXD may offer us a powerful and general algorithm for describing kinetics and thermodynamics in chemical and biochemical systems.

show abstract

Fluctuation power spectra reveal dynamical heterogeneity of peptides

Cited by 4 publications

References 29 publications

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

Effect of external pulling forces on the length distribution of peptides

Peptide kinetics from picoseconds to microseconds using boxed molecular dynamics: Power law rate coefficients in cyclisation reactions

Contact Info

Product

Resources

About