An effective all-atom potential for proteins

Irbäck, Anders; Mitternacht, Simon; Mohanty, Sandipan

doi:10.1186/1757-5036-2-2

Cited by 69 publications

(154 citation statements)

References 61 publications

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“…28 This study found that the isolated peptide folds in a cooperative manner, and that the number of native H bonds present, n hb , is a useful folding coordinate that has a bimodal distribution at the melting temperature. Figure 1a shows the free energy of the isolated GB1m3, calculated as a function of the two slowest TICA coordinates, TIC0 and TIC1.…”

Section: A Free-energy Landscapesmentioning

confidence: 99%

“…The potential is an effective energy function, parameterized through folding thermodynamics studies for a structurally diverse set of peptides and small proteins. 28 Previous applications of the model include folding/unfolding studies of several proteins with >90 residues. [29][30][31][32][33][34] Recently, it was used by us to simulate the peptides trp-cage and GB1m3 in the presence of protein crowders.…”

Section: B Biophysical Modelmentioning

confidence: 99%

“…28 In brief, the potential consists of four main terms, E = E loc + E ev + E hb + E sc . One term (E loc ) represents local interactions between atoms separated by only a few covalent bonds.…”

Section: B Biophysical Modelmentioning

confidence: 99%

“…Our simulations are based on an all-atom protein representation with torsional degrees of freedom, and an implicit solvent force field, 28 A detailed description of the interaction potential can be found elsewhere. 28 In brief, the potential consists of four main terms, E = E loc + E ev + E hb + E sc .…”

Section: B Biophysical Modelmentioning

confidence: 99%

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Markov modeling of peptide folding in the presence of protein crowders

Nilsson

Mohanty

Irbäck

2018

The Journal of Chemical Physics

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We use Markov state models (MSMs) to analyze the dynamics of a β-hairpin-forming peptide in Monte Carlo (MC) simulations with interacting protein crowders, for two different types of crowder proteins [bovine pancreatic trypsin inhibitor (BPTI) and GB1]. In these systems, at the temperature used, the peptide can be folded or unfolded and bound or unbound to crowder molecules. Four or five major freeenergy minima can be identified. To estimate the dominant MC relaxation times of the peptide, we build MSMs using a range of different time resolutions or lag times. We show that stable relaxation-time estimates can be obtained from the MSM eigenfunctions through fits to autocorrelation data. The eigenfunctions remain sufficiently accurate to permit stable relaxation-time estimation down to small lag times, at which point simple estimates based on the corresponding eigenvalues have large systematic uncertainties. The presence of the crowders have a stabilizing effect on the peptide, especially with BPTI crowders, which can be attributed to a reduced unfolding rate k u , while the folding rate k f is left largely unchanged.

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Section: A Free-energy Landscapesmentioning

confidence: 99%

Section: B Biophysical Modelmentioning

confidence: 99%

Section: B Biophysical Modelmentioning

confidence: 99%

Section: B Biophysical Modelmentioning

confidence: 99%

See 2 more Smart Citations

Markov modeling of peptide folding in the presence of protein crowders

Nilsson

Mohanty

Irbäck

2018

The Journal of Chemical Physics

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“…For all simulations in this paper we used the PROFASI force field, which has been shown to enable the reversible folding of peptides and small proteins (28). We selected two proteins, Ubiquitin and GB3, that do not fold using the force field alone, due to limitations in PROFASI.…”

Section: Using Chemical Shifts To Bias the Sampling By Changing The Fmentioning

confidence: 99%

Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts

Boomsma

Tian

Frellsen

et al. 2014

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

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Methods of protein structure determination based on NMR chemical shifts are becoming increasingly common. The most widely used approaches adopt the molecular fragment replacement strategy, in which structural fragments are repeatedly reassembled into different complete conformations in molecular simulations. Although these approaches are effective in generating individual structures consistent with the chemical shift data, they do not enable the sampling of the conformational space of proteins with correct statistical weights. Here, we present a method of molecular fragment replacement that makes it possible to perform equilibrium simulations of proteins, and hence to determine their free energy landscapes. This strategy is based on the encoding of the chemical shift information in a probabilistic model in Markov chain Monte Carlo simulations. First, we demonstrate that with this approach it is possible to fold proteins to their native states starting from extended structures. Second, we show that the method satisfies the detailed balance condition and hence it can be used to carry out an equilibrium sampling from the Boltzmann distribution corresponding to the force field used in the simulations. Third, by comparing the results of simulations carried out with and without chemical shift restraints we describe quantitatively the effects that these restraints have on the free energy landscapes of proteins. Taken together, these results demonstrate that the molecular fragment replacement strategy can be used in combination with chemical shift information to characterize not only the native structures of proteins but also their conformational fluctuations.

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Conformations of Betanova in aqueous trifluoroethanol

Chagolla

Gerig

2010

Biopolymers

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Conformations of the designed peptide Betanova in 42% trifluoroethanol/water (v/v) were explored. Circular dichroism (CD) observations provided no evidence for the presence of significant amounts of beta-structures in water, in TFE/water, or in ethanol/water. Nuclear magnetic resonance (NMR) diffusion experiments showed no significant difference in the hydrodynamic radius of the peptide in water and in 42% TFE/water. However, calculations indicated that the hydrodynamic radii of the triple-stranded beta-sheet, originally proposed for Betanova by Kortemme et al. (Science 1998, 281, 253-256), and a variety of partially folded forms of Betanova would be similar and likely could not be convincingly distinguished by diffusion experiments. Temperature coefficients (Deltadelta/DeltaT) of the peptide N--H chemical shifts are similar in water and 42% TFE/water, implying that most of these protons are highly solvent exposed in both solvents and likely do not participate in intramolecular hydrogen bonding interactions. Possible exceptions to this conclusion are the Lys9 and Lys15 residues, where a more positive coefficient may indicate that these residues are involved to some extent in local turn structures. Peptide proton-solvent fluorine intermolecular nuclear Overhauser effect (NOE)s at 25 degrees C were consistent with the presence of a mixture of conformations, which could include the triple-stranded beta-sheet structure as a minor component. At 0 degrees C, peptide-TFE NOEs indicated that TFE interacts strongly enough with many protons of Betanova that alcohol-peptide interactions persist for times of the order of nanoseconds, appreciably longer than the encounter time characteristic of mutual diffusion of TFE and the solute.

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An effective all-atom potential for proteins

Cited by 69 publications

References 61 publications

Markov modeling of peptide folding in the presence of protein crowders

Markov modeling of peptide folding in the presence of protein crowders

Equilibrium simulations of proteins using molecular fragment replacement and NMR chemical shifts

Conformations of Betanova in aqueous trifluoroethanol

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