Heterogeneous dynamics in partially disordered proteins

Virtanen, Salla I.; Kiirikki, Anne; Mikula, Kornelia M.; Iwaï, Hideo; Ollila, O. H. Samuli

doi:10.1039/d0cp03473h

Cited by 23 publications

(47 citation statements)

References 89 publications

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“…On the other hand, increasing number of studies suggest that properties of water model are critical in many applications of MD simulations, such as studies of protein dynamics 53 and conformational ensembles of disordered proteins. 54,55 Therefore, using the state of the art water models during the systematic parametrization of force fields would most likely not only improve the description of monolayer behavior, but also facilitate other applications of MD simulations. TIPS3P model used in the original CHARMM36/LJ-PME, 2,3 we repeated the simulations with two additional water models, namely OPC4 and TIP4P/05, since they best described the surface tension of water.…”

Section: Discussionmentioning

confidence: 99%

Accurate Simulations of Lipid Monolayers Require a Water Model With Correct Surface Tension

Tempra

Ollila

Javanainen

2021

Preprint

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Lipid monolayers provide our lungs and eyes their functionality, and serve as proxy systems in biomembrane research. Therefore, lipid monolayers have been studied intensively also using molecular dynamics simulations, which are able to probe their lateral structure and interactions with, e.g., pharmaceuticals or nanoparticles. However, such simulations have struggled in describing the forces at the air–water interface. Particularly the surface tension of water and long-range van der Waals interactions have been considered critical, but their importance in monolayer simulations has been evaluated only separately. Here we combine the recent C36/LJ-PME lipid force field that in- cludes long-range van der Waals forces with water models that reproduce experimental surface tensions to elucidate the importance of these contributions in monolayer simulations. Our results suggest that a water model with correct surface tension is necessary to reproduce experimental surface pressure–area isotherms and monolayer phase behavior, while standard cutoff-based CHARMM36 lipid model with the 4-point OPC water model still provides the best agreement with experiments. Our results emphasize the importance of using high quality water models in applications and parameter development in molecular dynamics simulations of biomolecules.

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Section: Discussionmentioning

confidence: 99%

Accurate Simulations of Lipid Monolayers Require a Water Model With Correct Surface Tension

Tempra

Ollila

Javanainen

2021

Preprint

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“…Recent versions of these force-fields (e.g., [49] , [50] , [51] , [52] ) have been introduced to mitigate these effects. In particular, a balanced description of protein-water interactions thanks to new water models [53] or rescaling approaches [54] have been shown to be critical for improving the description of disordered proteins [51] , [55] .…”

Section: An Overview Of Computational Approachesmentioning

confidence: 99%

“…Although linkers can be very long, they typically involve from 2 up to

30 residues [94] , [95] , displaying high levels of flexibility and absence of permanent secondary structure. MD simulations in combination with 15 N NMR relaxation experiments have shown that this flexibility occurs in a broad range of timescales [55] .…”

Section: Interactions Of Structured Domains Mediated or Regulated By Disordered Linkersmentioning

confidence: 99%

The diversity of molecular interactions involving intrinsically disordered proteins: A molecular modeling perspective

Clerc

Sagar

Barducci

et al. 2021

Computational and Structural Biotechnology Journal

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Intrinsically Disordered Proteins and Regions (IDPs/IDRs) are key components of a multitude of biological processes. Conformational malleability enables IDPs/IDRs to perform very specialized functions that cannot be accomplished by globular proteins. The functional role for most of these proteins is related to the recognition of other biomolecules to regulate biological processes or as a part of signaling pathways. Depending on the extent of disorder, the number of interacting sites and the type of partner, very different architectures for the resulting assemblies are possible. More recently, molecular condensates with liquid-like properties composed of multiple copies of IDPs and nucleic acids have been proven to regulate key processes in eukaryotic cells. The structural and kinetic details of disordered biomolecular complexes are difficult to unveil experimentally due to their inherent conformational heterogeneity. Computational approaches, alone or in combination with experimental data, have emerged as unavoidable tools to understand the functional mechanisms of this elusive type of assemblies. The level of description used, all-atom or coarse-grained, strongly depends on the size of the molecular systems and on the timescale of the investigated mechanism. In this mini-review, we describe the most relevant architectures found for molecular interactions involving IDPs/IDRs and the computational strategies applied for their investigation.

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“…Perrez-Borrajero et al [99] , [100] recently described the DNA binding behavior of C-terminal and N-terminal Pax5 paired domains by integrative NMR and dynamic cross-correlation matrices (DCCMs) from MD simulations that describe correlations of backbone motions on a residue basis. Virtanen et al [101] combined MD simulations and backbone 15 N-spin relaxation data to derive structural ensembles of the Engrailed 2 transcription factor. Further, Barros et al [102] compared the wild-type of tumor suppressor p53 with a Y220C mutant, employing Markov state models (MSM) and time-lagged independent components analysis (tICA).…”

Section: Combining Nmr and MD Simulationsmentioning

confidence: 99%

How to assess the structural dynamics of transcription factors by integrating sparse NMR and EPR constraints with molecular dynamics simulations

Kozak

Kurzbach

2021

Computational and Structural Biotechnology Journal

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Heterogeneous dynamics in partially disordered proteins

Abstract: Importance of disordered protein regions is increasingly recognized in biology, but their characterization remains challenging due to the lack of suitable experimental and theoretical methods. NMR experiments can detect multiple...

Cited by 23 publications

References 89 publications

Accurate Simulations of Lipid Monolayers Require a Water Model With Correct Surface Tension

Accurate Simulations of Lipid Monolayers Require a Water Model With Correct Surface Tension

The diversity of molecular interactions involving intrinsically disordered proteins: A molecular modeling perspective

How to assess the structural dynamics of transcription factors by integrating sparse NMR and EPR constraints with molecular dynamics simulations

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