Monte Carlo Approaches to the Protein Folding Problem

Skolnick, Jeffrey; Koliński, Andrzej

doi:10.1002/9780470141649.ch7

Cited by 10 publications

(2 citation statements)

References 255 publications

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“…The incorporation of the i/i15 and i/i16 terms induces correlation among the states of three successive residues along the peptide backbone, hence restricting the size of the accessible conformational space of the peptide significantly. This, in turn, promotes chain stiffness, contributes to its stability, and induces protein-like behavior (Skolnick and Kolinski, 1999;Pappu et al, 2000).…”

Section: Effective Energymentioning

confidence: 99%

Monte Carlo Studies of Folding, Dynamics, and Stability in α-Helices

Shental-Bechor

Kirca

Ben‐Tal

et al. 2005

Biophysical Journal

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Folding simulations of polyalanine peptides were carried out using an off-lattice Monte Carlo simulation technique. The peptide was represented as a chain of residues, each of which contains two interaction sites: one corresponding to the C(alpha) atom and the other to the side chain. A statistical potential was used to describe the interaction between these sites. The preferred conformations of the peptide chain on the energy surface, starting from several initial conditions, were searched by perturbations on its generalized coordinates with the Metropolis criterion. We observed that, at low temperatures, the effective energy was low and the helix content high. The calculated helix propagation (s) and nucleation (sigma) parameters of the Zimm-Bragg model were in reasonable agreement with the empirical data. Exploration of the energy surface of the alanine-based peptides (AAQAA)(3) and AAAAA(AAARA)(3)A demonstrated that their behavior is similar to that of polyalanine, in regard to their effective energy, helix content, and the temperature-dependence of their helicity. In contrast, stable secondary structures were not observed for (Gly)(20) at similar temperatures, which is consistent with the nonfolder nature of this peptide. The fluctuations in the slowest dynamics mode, which describe the elastic behavior of the chain, showed that as the temperature decreases, the polyalanine peptides become stiffer and retain conformations with higher helix content. Clustering of conformations during the folding phase implied that polyalanine folds into a helix through fewer numbers of intermediate conformations as the temperature decreases.

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Section: Effective Energymentioning

confidence: 99%

Monte Carlo Studies of Folding, Dynamics, and Stability in α-Helices

Shental-Bechor

Kirca

Ben‐Tal

et al. 2005

Biophysical Journal

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“…Previous approaches can be roughly grouped into two categories. The first strategy utilizes discrete conformational space, such as the use of lattice models ,, or discrete torsion-angle values in Monte Carlo sampling, to overcome entropic barriers. The second strategy aims at reducing the dimensionality of sampling space; this leads to reduced protein models at residue-level representations.…”

Section: Introductionmentioning

confidence: 99%

Balancing Simulation Accuracy and Efficiency with the Amber United Atom Force Field

Hsieh

Luo

2010

J. Phys. Chem. B

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We have analyzed the quality of a recently proposed Amber united-atom model and its overall efficiency in ab initio folding and thermodynamic sampling of two stable beta-hairpins. It is found that the mean backbone structures are quite consistent between the simulations in the united-atom and its corresponding all-atom models in Amber. More importantly, the simulated beta turns are also consistent between the two models. Finally, the chemical shifts on H alpha are highly consistent between simulations in the two models, although the simulated chemical shifts are lower than experiment, indicating less structured peptides, probably due to the omission of the hydrophobic term in the simulations. More interestingly, the stabilities of both beta-hairpins at room temperature are similar to those derived from the NMR measurement, whether the united-atom or the all-atom model is used. Detailed analysis shows high percentages of backbone torsion angles within the beta region and high percentages of native contacts. Given the reasonable quality of the united-atom model with respect to experimental data, we have further studied the simulation efficiency of the united-atom model over the all-atom model. Our data shows that the united-atom model is a factor of 6-8 faster than the all-atom model as measured with the ab initio first pass folding time for the two tested beta-hairpins. Detailed structural analysis shows that all ab initio folded trajectories enter the native basin, whether the united-atom model or the all-atom model is used. Finally, we have also studied the simulation efficiency of the united-atom model as measured in terms of how fast thermodynamic convergence can be achieved. It is apparent that the united-atom simulations reach convergence faster than the all-atom simulations with respect to both mean potential energies and mean native contacts. These findings show that the efficiency of the united-atom model is clearly beyond the per-step dynamics simulation of about 2 over the all-atom model. Thus, reasonable reduction of a protein model can be achieved with improved sampling efficiency while still preserving a high level of accuracy for applications in both ab initio folding and thermodynamic sampling. This study motivates us to develop more simplified protein models with sufficient consistency with the all-atom models for enhanced conformational sampling.

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