The Influence of Macromolecular Crowding on HIV-1 Protease Internal Dynamics

Minh, David D. L.; Chang, Chia‐en A.; Trylska, Joanna; Tozzini, Valentina; McCammon, J. Andrew

doi:10.1021/ja060483s

Cited by 94 publications

(127 citation statements)

References 25 publications

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“…[32][33][34][35][36][37][38] In many cases, the crowders have been modeled as hard spheres. To enable more detailed simulations, a post-processing alternative to direct simulation has been developed.…”

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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“…[2][3][4][5] Macromolecular crowding can also reduce protein diffusion rate, 6 enhances the folding of marginally stable proteins, 7 changes protein shape and structure, [8][9][10] and affects protein dynamics. 11,12 In particular, confinement has been widely used to study crowding effects. Two common methods to introduce confinement include using sol-gel silica glass and reverse micelles.…”

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confidence: 99%

Simulations of the confinement of ubiquitin in self-assembled reverse micelles

Tian

Garcı́a

2011

The Journal of Chemical Physics

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We describe the effects of confinement on the structure, hydration, and the internal dynamics of ubiquitin encapsulated in reverse micelles (RM). We performed molecular dynamics simulations of the encapsulation of ubiquitin into self-assembled protein/surfactant reverse micelles to study the positioning and interactions of the protein with the RM and found that ubiquitin binds to the RM interface at low salt concentrations. The same hydrophobic patch that is recognized by ubiquitin binding domains in vivo is found to make direct contact with the surfactant head groups, hydrophobic tails, and the iso-octane solvent. The fast backbone N-H relaxation dynamics show that the fluctuations of the protein encapsulated in the RM are reduced when compared to the protein in bulk. This reduction in fluctuations can be explained by the direct interactions of ubiquitin with the surfactant and by the reduced hydration environment within the RM. At high concentrations of excess salt, the protein does not bind strongly to the RM interface and the fast backbone dynamics are similar to that of the protein in bulk. Our simulations demonstrate that the confinement of protein can result in altered protein dynamics due to the interactions between the protein and the surfactant.

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“…In spite of this general picture, most computer simulations have investigated the stability of and binding between compact proteins in cellmimicking environments composed of passively diffusing and inert macromolecules (Cheung et al 2005;Minh et al 2006;Ridgway et al 2008;Wieczorek and Zielenkiewicz 2008;Wojciechowski and Cieplak 2008;Mittal and Best 2010;Wojciechowski et al 2010;Wang and Cheung 2012;Denesyuk and Thirumalai 2013;Qi et al 2014;Naddaf and Sayyed-Ahmad 2014;Starzyk et al 2016;Yu et al 2016).…”

Section: Toward Realistic Molecular Simulations Of Cellular Eventsmentioning

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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The Influence of Macromolecular Crowding on HIV-1 Protease Internal Dynamics

Cited by 94 publications

References 25 publications

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

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

Simulations of the confinement of ubiquitin in self-assembled reverse micelles

Molecular simulations of cellular processes

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