Molecular Dynamics Simulations Combined with Nuclear Magnetic Resonance and/or Small-Angle X-ray Scattering Data for Characterizing Intrinsically Disordered Protein Conformational Ensembles

2019 ◽  
Vol 59 (5) ◽  
pp. 1743-1758 ◽  
Author(s):  
Maud Chan-Yao-Chong ◽  
Dominique Durand ◽  
Tâp Ha-Duong
Keyword(s):  
Molecular Dynamics ◽  
Nuclear Magnetic Resonance ◽  
Intrinsically Disordered Protein ◽  
Scattering Data ◽  
X Ray ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
X Ray Scattering ◽  
Dynamics Simulations

scholarly journals Improving the global dimensions of intrinsically disordered proteins in Martini 3

2021 ◽  
Author(s):  
F. Emil Thomasen ◽  
Francesco Pesce ◽  
Mette Ahrensback Roesgaard ◽  
Giulio Tesei ◽  
Kresten Lindorff-Larsen
Keyword(s):  
Molecular Dynamics ◽  
Intrinsically Disordered Proteins ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
Saxs Data ◽  
X Ray ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
X Ray Scattering ◽  
Dynamics Simulations

AbstractCoarse-grained molecular dynamics simulations are a useful tool to determine conformational ensembles of intrinsically disordered proteins (IDPs). Here, we show that the coarse-grained force field Martini 3 underestimates the global dimensions of IDPs when compared with small angle X-ray scattering (SAXS) data. Increasing the strength of protein-water interactions favors more expanded conformations, improving agreement with SAXS data and alleviating problems with overestimated IDP-IDP interactions.

scholarly journals Conformational Ensembles of an Intrinsically Disordered Protein pKID with and without a KIX Domain in Explicit Solvent Investigated by All-Atom Multicanonical Molecular Dynamics

Biomolecules ◽  
2012 ◽  
Vol 2 (1) ◽  
pp. 104-121 ◽  
Author(s):  
Koji Umezawa ◽  
Jinzen Ikebe ◽  
Mitsunori Takano ◽  
Haruki Nakamura ◽  
Junichi Higo
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Binding Site ◽  
Complex Structure ◽  
Intrinsically Disordered Protein ◽  
Bound State ◽  
Conformational Ensembles ◽  
Intrinsically Disordered ◽  
Dynamics Simulations ◽  
High Flexibility

The phosphorylated kinase-inducible activation domain (pKID) adopts a helix–loop–helix structure upon binding to its partner KIX, although it is unstructured in the unbound state. The N-terminal and C-terminal regions of pKID, which adopt helices in the complex, are called, respectively, αA and αB. We performed all-atom multicanonical molecular dynamics simulations of pKID with and without KIX in explicit solvents to generate conformational ensembles. Although the unbound pKID was disordered overall, αA and αB exhibited a nascent helix propensity; the propensity of αA was stronger than that of αB, which agrees with experimental results. In the bound state, the free-energy landscape of αB involved two low free-energy fractions: native-like and non-native fractions. This result suggests that αB folds according to the induced-fit mechanism. The αB-helix direction was well aligned as in the NMR complex structure, although the αA helix exhibited high flexibility. These results also agree quantitatively with experimental observations. We have detected that the αB helix can bind to another site of KIX, to which another protein MLL also binds with the adopting helix. Consequently, MLL can facilitate pKID binding to the pKID-binding site by blocking the MLL-binding site. This also supports experimentally obtained results.

Molecular dynamics simulations of the intrinsically disordered protein amelogenin

2016 ◽  
Vol 35 (8) ◽  
pp. 1813-1823 ◽  
Author(s):  
Alessandra Apicella ◽  
Matteo Marascio ◽  
Vincenzo Colangelo ◽  
Monica Soncini ◽  
Alfonso Gautieri ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Intrinsically Disordered Protein ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Dynamics Simulations

Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau

2015 ◽  
Vol 119 (39) ◽  
pp. 12580-12589 ◽  
Author(s):  
Yann Fichou ◽  
Matthias Heyden ◽  
Giuseppe Zaccai ◽  
Martin Weik ◽  
Douglas J. Tobias
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Intrinsically Disordered Protein ◽  
Protein Tau ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Dynamics Simulations

scholarly journals Extreme Fuzzy Association of an Intrinsically Disordered Protein with Acidic Membranes

2020 ◽  
Author(s):  
Alan Hicks ◽  
Cristian A. Escobar ◽  
Timothy A. Cross ◽  
Huan-Xiang Zhou
Keyword(s):  
Molecular Dynamics ◽  
Solid State Nmr ◽  
Transmembrane Helix ◽  
Intrinsically Disordered Protein ◽  
Membrane Association ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Protein ◽  
Membrane Tethering ◽  
Dynamics Simulations

AbstractMany physiological and pathophysiological processes, including Mycobacterium tuberculosis (Mtb) cell division, may involve fuzzy membrane association by proteins via intrinsically disordered regions. The fuzziness is extreme when the conformation and pose of the bound protein and the composition of the proximal lipids are all highly dynamic. Here we tackled the challenge in characterizing the extreme fuzzy membrane association of the disordered, cytoplasmic N-terminal region (NT) of ChiZ, an Mtb divisome protein, by combining solution and solid-state NMR spectroscopy and molecular dynamics simulations. In a typical pose, NT is anchored to acidic membranes by Arg residues in the midsection. Competition for Arg interactions between lipids and acidic residues, all in the first half of NT, makes the second half more prominent in membrane association. This asymmetry is accentuated by membrane tethering of the downstream transmembrane helix. These insights into sequence-interaction relations may serve as a paradigm for understanding fuzzy membrane association.

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