Atomistic molecular dynamics simulations of ATP-binding cassette transporters

2016 ◽  
Vol 6 (3) ◽  
pp. 255-265 ◽  
Author(s):  
Hui Liu ◽  
Dan Li ◽  
Youyong Li ◽  
Tingjun Hou
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Atp Binding ◽  
Atp Binding Cassette Transporters ◽  
Dynamics Simulations ◽  
Atp Binding Cassette

scholarly journals Molecular modelling of the nucleotide-binding domain of Wilson's disease protein: location of the ATP-binding site, domain dynamics and potential effects of the major disease mutations

2004 ◽  
Vol 382 (1) ◽  
pp. 293-305 ◽  
Author(s):  
Roman G. EFREMOV ◽  
Yuri A. KOSINSKY ◽  
Dmitry E. NOLDE ◽  
Ruslan TSIVKOVSKII ◽  
Alexander S. ARSENIEV ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Molecular Modelling ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Binding Domain ◽  
Atp Binding ◽  
Disease Mutations ◽  
Disease Protein ◽  
Dynamics Simulations

WNDP (Wilson's disease protein) is a copper-transporting ATPase that plays an essential role in human physiology. Mutations in WNDP result in copper accumulation in tissues and cause a severe hepato-neurological disorder known as Wilson's disease. Several mutations were surmised to affect the nucleotide binding and hydrolysis by WNDP; however, how the nucleotides bind to normal and mutated WNDP remains unknown. To aid such studies, we performed the molecular modelling of the spatial structure and dynamics of the ATP-binding domain of WNDP and its interactions with ATP. The three-dimensional models of this domain in two conformations were built using the X-ray structures of the Ca2+-ATPase in the E1 and E2 states. To study the functional aspects of the models, they were subjected to long-term molecular dynamics simulations in an explicit solvent; similar calculations were performed for the ATP-binding domain of Ca2+-ATPase. In both cases, we found large-scale motions that lead to significant changes of distances between several functionally important residues. The ATP docking revealed two possible modes of ATP binding: via adenosine buried in the cleft near residues H1069, R1151 and D1164, and via phosphate moiety ‘anchored’ by H-bonds with residues in the vicinity of catalytic D1027. Furthermore, interaction of ATP with both sites occurs if they are spatially close to each other. This may be achieved after relative domain motions of the ‘closure’ type observed in molecular dynamics simulations. The results provide a framework for analysis of disease mutations and for future mutagenesis studies.

scholarly journals Conformational Change of F1-ATPase ε Subunit upon ATP Binding Studied by Molecular Dynamics Simulations and Small-angle X-ray Scattering

2009 ◽  
Vol 96 (3) ◽  
pp. 299a
Author(s):  
Tomotaka Oroguchi ◽  
Yasuyuki Kato-Yamada ◽  
Hiroshi Hashimoto ◽  
Satoru Unzai ◽  
Mamoru Sato ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Conformational Change ◽  
Small Angle ◽  
Atp Binding ◽  
X Ray ◽  
F1 Atpase ◽  
X Ray Scattering ◽  
Dynamics Simulations ◽  
Ray Scattering

The Power Stroke Driven by ATP Binding in CFTR As Studied by Molecular Dynamics Simulations

2012 ◽  
Vol 117 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Tomoka Furukawa-Hagiya ◽  
Tadaomi Furuta ◽  
Shuntaro Chiba ◽  
Yoshiro Sohma ◽  
Minoru Sakurai
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Power Stroke ◽  
Atp Binding ◽  
Dynamics Simulations
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