| 1. |
- Favrin, Giorgio, et al.
(författare)
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Folding of a small helical protein using hydrogen bonds and hydrophobicity forces.
- 2002
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Ingår i: Proteins. - : Wiley. - 0887-3585. ; 47:2, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- A reduced protein model with five to six atoms per amino acid and five amino acid types is developed and tested on a three-helix-bundle protein, a 46-amino acid fragment from staphylococcal protein A. The model does not rely on the widely used Go approximation, which ignores non-native interactions. We find that the collapse transition is considerably more abrupt for the protein A sequence than for random sequences with the same composition. The chain collapse is found to be at least as fast as helix formation. Energy minimization restricted to the thermodynamically favored topology gives a structure that has a root-mean-square deviation of 1.8 A from the native structure. The sequence-dependent part of our potential is pairwise additive. Our calculations suggest that fine-tuning this potential by parameter optimization is of limited use.
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| 2. |
- Favrin, Giorgio, et al.
(författare)
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Monte Carlo update for chain molecules: Biased Gaussian steps in torsional space
- 2001
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 114:8, s. 8154-8158
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Tidskriftsartikel (refereegranskat)abstract
- We develop a new elementary move for simulations of polymer chains in torsion angle space. The method is flexible and easy to implement. Tentative updates are drawn from a (conformation-dependent) Gaussian distribution that favors approximately local deformations of the chain. The degree of bias is controlled by a parameter b. The method is tested on a reduced model protein with 54 amino acids and the Ramachandran torsion angles as its only degrees of freedom, for different b. Without excessive fine tuning, we find that the effective step size can be increased by a factor of 3 compared to the unbiased b = 0 case. The method may be useful for kinetic studies, too.
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| 3. |
- Favrin, Giorgio, et al.
(författare)
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Oligomerization of amyloid A beta(16-22) peptides using hydrogen bonds and hydrophobicity forces
- 2004
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Ingår i: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 87:6, s. 3657-3664
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Tidskriftsartikel (refereegranskat)abstract
- The 16 - 22 amino-acid fragment of the beta-amyloid peptide associated with the Alzheimer's disease, Abeta, is capable of forming amyloid fibrils. Here we study the aggregation mechanism of Abeta(16-22) peptides by unbiased thermodynamic simulations at the atomic level for systems of one, three, and six Abeta(16-22) peptides. We find that the isolated Abeta(16-22) peptide is mainly a random coil in the sense that both the alpha-helix and beta-strand contents are low, whereas the three- and six-chain systems form aggregated structures with a high beta-sheet content. Furthermore, in agreement with experiments on Abeta(16-22) fibrils, we find that large parallel beta-sheets are unlikely to form. For the six-chain system, the aggregated structures can have many different shapes, but certain particularly stable shapes can be identified.
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| 4. |
- Favrin, Giorgio, et al.
(författare)
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Sequence-based study of two related proteins with different folding behaviors
- 2004
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Ingår i: Proteins. - : Wiley. - 0887-3585. ; 54:1, s. 8-12
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Tidskriftsartikel (refereegranskat)abstract
- Z(SPA-1) is an engineered protein that binds to its parent, the three-helix-bundle Z domain of staphylococcal protein A. Uncomplexed Z(SPA-1) shows a reduced helix content and a melting behavior that is less cooperative, compared with the wild-type Z domain. Here we show that the difference in folding behavior between these two sequences can be partly understood in terms of an off-lattice model with 5-6 atoms per amino acid and a minimalistic potential, in which folding is driven by backbone hydrogen bonding and effective hydrophobic attraction. (C) 2003 Wiley-Liss, Inc.
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| 5. |
- Favrin, Giorgio, et al.
(författare)
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Two-state folding over a weak free-energy barrier
- 2003
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Ingår i: Biophysical Journal. - 1542-0086. ; 85:3, s. 1457-1465
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Tidskriftsartikel (refereegranskat)abstract
- We present a Monte Carlo study of a model protein with 54 amino acids that folds directly to its native three-helix-bundle state without forming any well-defined intermediate state. The free-energy barrier separating the native and unfolded states of this protein is found to be weak, even at the folding temperature. Nevertheless, we find that melting curves to a good approximation can be described in terms of a simple two-state system, and that the relaxation behavior is close to single exponential. The motion along individual reaction coordinates is roughly diffusive on timescales beyond the reconfiguration time for a single helix. A simple estimate based on diffusion in a square-well potential predicts the relaxation time within a factor of two.
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| 6. |
- Gupta, N, et al.
(författare)
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Coupled folding-binding versus docking: A lattice model study
- 2004
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 120:8, s. 3983-3989
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Tidskriftsartikel (refereegranskat)abstract
- Using a simple hydrophobic/polar protein model, we perform a Monte Carlo study of the thermodynamics and kinetics of binding to a target structure for two closely related sequences, one of which has a unique folded state while the other is unstructured. We obtain significant differences in their binding behavior. The stable sequence has rigid docking as its preferred binding mode, while the unstructured chain tends to first attach to the target and then fold. The free-energy profiles associated with these two binding modes are compared. (C) 2004 American Institute of Physics.
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| 7. |
- Irbäck, Anders
(författare)
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A minimalistic all-atom approach to protein folding
- 2003
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Ingår i: Journal of Physics: Condensed Matter. - : IOP Publishing. - 1361-648X .- 0953-8984. ; 15:18, s. 1797-1807
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Tidskriftsartikel (refereegranskat)abstract
- Using simple sequence-based potentials, the folding properties of a designed three-helix-bundle protein, an alpha-helix and a beta-hairpin are studied. The three-helix-bundle protein is modelled using 5-6 atoms per amino acid and is found to undergo a first-order-like folding transition in which chain collapse and helix formation cannot be separated, which is in-accord with experimental data. The other two sequences are studied using a model that contains all atoms and are indeed found to make an alpha-helix and a beta-hairpin, respectively, for exactly the same choice of parameters. The calculated melting curves are, moreover, in reasonable quantitative agreement with experimental data, for both peptides. The melting curves are found to be quite well described by a simple two-state model, although the energy distributions lack a clear bimodal shape.
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| 8. |
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| 9. |
- Irbäck, Anders, et al.
(författare)
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Folding thermodynamics of three beta-sheet peptides: A model study
- 2004
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Ingår i: Proteins. - : Wiley. - 0887-3585. ; 56:1, s. 110-116
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Tidskriftsartikel (refereegranskat)abstract
- We study the folding thermodynamics of a beta-hairpin and two three-stranded beta-sheet peptides using a simplified sequence-based all-atom model, in which folding is driven mainly by backbone hydrogen bonding and effective hydrophobic attraction. The native populations obtained for these three sequences are in good. agreement with experimental data. We also show that the apparent native population depends on which observable is studied; the hydrophobicity energy and the number of native hydrogen bonds give different results. The magnitude of this dependence matches well with the results obtained in two different experiments on the beta-hairpin. (C) 2004 Wiley-Liss, Inc.
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| 10. |
- Irbäck, Anders
(författare)
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Protein folding in the absence of a clear free-energy barrier
- 2003
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 34:10, s. 4867-4878
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Tidskriftsartikel (refereegranskat)abstract
- Many small proteins fold in a two-state manner, the rate-limiting step being the passage of the free-energy barrier separating the unfolded state from the native one. The free-energy barrier is, however, weak or absent for the fastest-folding proteins. Here a simple diffusion picture for such proteins is discussed. It is tested on a model protein that makes a three-helix bundle. Assuming the motion along individual reaction coordinates to be diffusive on timescales beyond the reconfiguration time for a single helix, it is found that the relaxation time can be predicted within a factor of two. It is also shown that melting curves for this protein to a good approximation can be described in terms of a simple two-state system, despite the absence of a clear free-energy barrier.
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| 11. |
- Irbäck, Anders
(författare)
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Sequence design in coarse-grained protein models
- 2000
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Ingår i: Progress of Theoretical Physics Supplement. ; 138, s. 273-281
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Konferensbidrag (refereegranskat)abstract
- Designing amino acid sequences that are stable in a given target structure amounts to maximizing a conditional probability. A straightforward approach to accomplish this is a nested Monte Carlo where the conformation space is explored over and over again for different fixed sequences. In this paper we discuss an alternative Monte Carlo approach, multisequence design, where conformation and sequence degrees of freedom are simultaneously probed. The method is explored on hydrophobic/polar models. A statistical analysis of sequence correlations is also discussed. It is found that hydrophobic/polar model sequences and enzymes display hydrophobicity correlations that are qualitatively similar.
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| 12. |
- Irbäck, Anders, et al.
(författare)
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Thermodynamics of α- and β-structure formation in proteins
- 2003
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Ingår i: Biophysical Journal. - 1542-0086. ; 85:3, s. 1466-1473
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Tidskriftsartikel (refereegranskat)abstract
- An atomic protein model with a minimalistic potential is developed and then tested on an α-helix and a β-hairpin, using exactly the same parameters for both peptides. We find that melting curves for these sequences to a good approximation can be described by a simple two-state model, with parameters that are in reasonable quantitative agreement with experimental data. Despite the apparent two-state character of the melting curves, the energy distributions are found to lack a clear bimodal shape, which is discussed in some detail. We also perform a Monte Carlo-based kinetic study and find, in accord with experimental data, that the α-helix forms faster than the β-hairpin.
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