Reaching new levels of realism in modeling biological macromolecules in cellular environments

Feig, Michael; Sugita, Yuji

doi:10.1016/j.jmgm.2013.08.017

Cited by 61 publications

(63 citation statements)

References 232 publications

(262 reference statements)

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“…How these factors influence proteinprotein interactions and biomolecular processes such as folding, binding, and aggregation is a topic attracting increasing interest. [1][2][3][4][5] It is well established that excluded-volume interactions with crowder particles can have a significant stabilizing effect on globular proteins, as demonstrated by experiments with synthetic crowding agents such as Ficoll or dextran. 6 Today, experiments are increasingly often performed under more realistic crowding conditions, using concentrated protein solutions [7][8][9][10] or cells.…”

Section: Introductionmentioning

confidence: 99%

Equilibrium simulation of trp-cage in the presence of protein crowders

Bille

Linse

Mohanty

et al. 2015

The Journal of Chemical Physics

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Link to publication Citation for published version (APA): Bille, A., Linse, B., Mohanty, S., & Irbäck, A. (2015). Equilibrium simulation of trp-cage in the presence of protein crowders. Journal of Chemical Physics, 143(17), [175102]. DOI: 10.1063/1.4934997General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. While steric crowders tend to stabilize globular proteins, it has been found that protein crowders can have an either stabilizing or destabilizing effect, where a destabilization may arise from nonspecific attractive interactions between the test protein and the crowders. Here, we use Monte Carlo replicaexchange methods to explore the equilibrium behavior of the miniprotein trp-cage in the presence of protein crowders. Our results suggest that the surrounding crowders prevent trp-cage from adopting its global native fold, while giving rise to a stabilization of its main secondary-structure element, an α-helix. With the crowding agent used (bovine pancreatic trypsin inhibitor), the trp-cage-crowder interactions are found to be specific, involving a few key residues, most of which are prolines. The effects of these crowders are contrasted with those of hard-sphere crowders. C 2015 AIP Publishing LLC. Equilibrium simulation of trp-cage in the presence of protein crowders[http://dx

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Section: Introductionmentioning

confidence: 99%

Equilibrium simulation of trp-cage in the presence of protein crowders

Bille

Linse

Mohanty

et al. 2015

The Journal of Chemical Physics

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“…A growing number of real-time measurements of how cell components (proteins, nucleic acids, lipids, and others) perform their functions is expected to be a further stimulus to construct new coarse-grained modeling tools, including whole-cell models. 54, 55,423 force fields for simulations of large biomacromolecular systems. She is also developing a new low resolution coarse-grained model for the long time multiscale modeling of proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The role of these nonspecific interactions is essential to the mechanisms of life and therefore actively investigated. 422 Cellular environments can be described at atomic resolution or using coarse-grained models at different levels of coarsegraining, 423 i.e. implicit solvent models, molecular-shape preserving coarse-grained models or spherical coarse-grained models of solute biomolecules.…”

Section: Simulations Of Protein Dynamicsmentioning

confidence: 99%

Coarse-Grained Protein Models and Their Applications

et al. 2016

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The traditional computational modeling of protein structure, dynamics, and interactions remains difficult for many protein systems. It is mostly due to the size of protein conformational spaces and required simulation time scales that are still too large to be studied in atomistic detail. Lowering the level of protein representation from all-atom to coarse-grained opens up new possibilities for studying protein systems. In this review we provide an overview of coarse-grained models focusing on their design, including choices of representation, models of energy functions, sampling of conformational space, and applications in the modeling of protein structure, dynamics, and interactions. A more detailed description is given for applications of coarse-grained models suitable for efficient combinations with all-atom simulations in multiscale modeling strategies.

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“…Ultimately, the goal is to simulate an entire cell (Tomita 2001;Feig and Sugita 2013). As an example of the complexity of this task, we have reported the success of different models in reproducing diffusion in E. coli, despite them using different assumptions and ingredients.…”

Section: Conclusion and Future Challengesmentioning

confidence: 99%

Molecular simulations of cellular processes

Trovato

Fumagalli

2017

Biophys Rev

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It is, nowadays, possible to simulate biological processes in conditions that mimic the different cellular compartments. Several groups have performed these calculations using molecular models that vary in performance and accuracy. In many cases, the atomistic degrees of freedom have been eliminated, sacrificing both structural complexity and chemical specificity to be able to explore slow processes. In this review, we will discuss the insights gained from computer simulations on macromolecule diffusion, nuclear body formation, and processes involving the genetic material inside cell-mimicking spaces. We will also discuss the challenges to generate new models suitable for the simulations of biological processes on a cell scale and for cellcycle-long times, including non-equilibrium events such as the co-translational folding, misfolding, and aggregation of proteins. A prominent role will be played by the wise choice of the structural simplifications and, simultaneously, of a relatively complex energetic description. These challenging tasks will rely on the integration of experimental and computational methods, achieved through the application of efficient algorithms.

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Reaching new levels of realism in modeling biological macromolecules in cellular environments

Cited by 61 publications

References 232 publications

Equilibrium simulation of trp-cage in the presence of protein crowders

Equilibrium simulation of trp-cage in the presence of protein crowders

Coarse-Grained Protein Models and Their Applications

Molecular simulations of cellular processes

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