Stepwise helix formation and chain compaction during protein folding

Röder, Heinrich

doi:10.1073/pnas.0308172101

Cited by 27 publications

(31 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both issues are not free from controversy [29,[39][40][41]. Based on NMR spectroscopy, a fourstate mechanism N → I 1 → I 2 → D has been suggested for apoMb where the I 1 state comprises the formation of the A, G, and H helices and the I 2 state is considered as a new stage in which the B segment is formed [42][43][44].…”

Section: Configurational and Hydration Entropies In Myoglobin's Denatmentioning

confidence: 99%

“…For this, we shall consider thermal denaturation of hydrated myoglobin (Mb, PDB:1MBN) as our probe system. Mb is a protein conformed by a prosthetic heme group and K = 153 residues integrated in a single polypeptide chain with molecular weight M w = 17,235 Da which folds into eight α-helices named from A to H [29,30]. Given that almost 80% of the native fold corresponds to α helical content [31], Mb's thermal denaturation can be considered in a good approximation as the unfolding of n =8 α-helices with a distribution of sizes {A 1 ,⋯, A 8 }, which range from A 3 = 4 aminoacid residues for the C-helix to A 8 = 25 aminoacid residues for the H-helix [32].…”

Section: Adam-gibbs Formulation For Hydrated Protein's Relaxationmentioning

confidence: 99%

See 1 more Smart Citation

Evidence of α fluctuations in myoglobin's denaturation in the high temperature region: Average relaxation time from an Adam–Gibbs perspective

Olivares‐Quiroz

García‐Colín

2009

Biophysical Chemistry

View full text Add to dashboard Cite

Section: Configurational and Hydration Entropies In Myoglobin's Denatmentioning

confidence: 99%

Section: Adam-gibbs Formulation For Hydrated Protein's Relaxationmentioning

confidence: 99%

Evidence of α fluctuations in myoglobin's denaturation in the high temperature region: Average relaxation time from an Adam–Gibbs perspective

Olivares‐Quiroz

García‐Colín

2009

Biophysical Chemistry

View full text Add to dashboard Cite

“…Focusing on this last domain, important structural events occur on a microsecond time scale [10]. To resolve folding events of order 10 microseconds, mixer designs are required that effect mixing in a few microseconds or less.…”

Section: Fast Microfluidic Protein Folding Devicesmentioning

confidence: 99%

Semi-deterministic and genetic algorithms for global optimization of microfluidic protein-folding devices

Ivorra

Hertzog

Mohammadi

et al. 2006

Int. J. Numer. Meth. Engng

View full text Add to dashboard Cite

-In this paper we reformulate global optimization problems in terms of boundary value problems (BVP). This allows us to introduce a new class of optimization algorithms. Indeed, current optimization methods, including non-deterministic ones, can be seen as discretizations of initial value problems for differential equations, or systems of differential equations. Furthermore, in order to reduce computational time approximate state and sensitivity evaluations are introduced during optimization. Lastly, we demonstrated the efficacy of two algorithms, included in the former class, on two academic test cases and on the design of a fast microfluidic protein folding device. The aim of the latter design is to reduce mixing times of proteins to microsecond timescales. Results are compared with those obtained with a classical genetic algorithm.

show abstract

“…C of amino acids) acquire the 3D shapes (called folded) enabling them to perform a wide range of biological functions. 1,2 The applications of protein folding in research and industry are numerous, including, drug discovery, DNA sequencing and amplification, molecular diagnostics, and food engineering (see, for instance, Refs. [3][4][5].…”

mentioning

confidence: 99%

Two- and three-dimensional modeling and optimization applied to the design of a fast hydrodynamic focusing microfluidic mixer for protein folding

et al. 2013

View full text Add to dashboard Cite

We present a design of a microfluidic mixer based on hydrodynamic focusing which is used to initiate the folding process (i.e., changes of the molecular structure) of a protein. The folding process is initiated by diluting (from 90% to 30%) the local denaturant concentration (initially 6 M GdCl solution) in a short time interval we refer to as mixing time. Our objective is to optimize this mixer by choosing suitable shape and flow conditions in order to minimize this mixing time. To this end, we first introduce a numerical model that enables computation of the mixing time of a mixer. This model is based on a finite element method approximation of the incompressible Navier-Stokes equations coupled with the convective diffusion equation. To reduce the computational time, this model is implemented in both full three-dimensional (3D) and simplified two-dimensional (2D) versions; and we analyze the ability of the 2D model to approximate the mixing time predicted by the 3D model. We found that the 2D model approximates the mixing time predicted by the 3D model with a mean error of about 15%, which is considered reasonable. Then, we define a mixer optimization problem considering the 2D model and solve it using a hybrid global optimization algorithm. In particular, we consider geometrical variables and injection velocities as optimization parameters. We achieve a design with a predicted mixing time of 0.10 μs, approximately one order of magnitude faster than previous mixer designs. This improvement can be in part explained by the new mixer geometry including an angle of π /5 radians at the channel intersection and injections velocities of 5.2 m s −1 and 0.038 m s −1 for the side and central inlet channels, respectively. Finally, we verify the robustness of the optimized result by performing a sensitivity analysis of its parameters considering the 3D model. During this study, the optimized mixer was demonstrated to be robust by exhibiting mixing time variations of the same order than the parameter ones. Thus, the obtained 2D design can be considered optimal also for the 3D model. C 2013 American Institute of Physics.

show abstract

Stepwise helix formation and chain compaction during protein folding

Cited by 27 publications

References 25 publications

Evidence of α fluctuations in myoglobin's denaturation in the high temperature region: Average relaxation time from an Adam–Gibbs perspective

Evidence of α fluctuations in myoglobin's denaturation in the high temperature region: Average relaxation time from an Adam–Gibbs perspective

Semi-deterministic and genetic algorithms for global optimization of microfluidic protein-folding devices

Two- and three-dimensional modeling and optimization applied to the design of a fast hydrodynamic focusing microfluidic mixer for protein folding

Contact Info

Product

Resources

About