scholarly journals X-interface is not the explanation for the slow disassembly of N-cadherin dimers in the apo state

2012 ◽  
Vol 21 (7) ◽  
pp. 1006-1014 ◽  
Author(s):  
Nagamani Vunnam ◽  
Susan Pedigo
Keyword(s):  
X Interface ◽  
Apo State

Metastable superconductivity of Mo/MoO3−x interface

2019 ◽  
Vol 558 ◽  
pp. 25-29 ◽  
Author(s):  
A.V. Palnichenko ◽  
I.I. Zver‘kova ◽  
D.V. Shakhrai ◽  
O.M. Vyaselev
Keyword(s):  
X Interface

Monitoring local order in the liquid-X interface

2021 ◽  
pp. e1875076
Author(s):  
Linsey Nowack ◽  
Stuart A. Rice
Keyword(s):  
Local Order ◽  
X Interface

scholarly journals Cryptic-site binding mechanism of medium-sized Bcl-xL inhibiting compounds elucidated by McMD-based dynamic docking simulations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gert-Jan Bekker ◽  
Ikuo Fukuda ◽  
Junichi Higo ◽  
Yoshifumi Fukunishi ◽  
Narutoshi Kamiya
Keyword(s):  
Ligand Binding ◽  
Cancer Progression ◽  
Hydrophobic Interactions ◽  
Binding Mechanism ◽  
Docking Simulations ◽  
Large Conformational Change ◽  
Binding Pockets ◽  
Dynamic Docking ◽  
Site Binding ◽  
Apo State

AbstractWe have performed multicanonical molecular dynamics (McMD) based dynamic docking simulations to study and compare the binding mechanism between two medium-sized inhibitors (ABT-737 and WEHI-539) that bind to the cryptic site of Bcl-xL, by exhaustively sampling the conformational and configurational space. Cryptic sites are binding pockets that are transiently formed in the apo state or are induced upon ligand binding. Bcl-xL, a pro-survival protein involved in cancer progression, is known to have a cryptic site, whereby the shape of the pocket depends on which ligand is bound to it. Starting from the apo-structure, we have performed two independent McMD-based dynamic docking simulations for each ligand, and were able to obtain near-native complex structures in both cases. In addition, we have also studied their interactions along their respective binding pathways by using path sampling simulations, which showed that the ligands form stable binding configurations via predominantly hydrophobic interactions. Although the protein started from the apo state, both ligands modulated the pocket in different ways, shifting the conformational preference of the sub-pockets of Bcl-xL. We demonstrate that McMD-based dynamic docking is a powerful tool that can be effectively used to study binding mechanisms involving a cryptic site, where ligand binding requires a large conformational change in the protein to occur.

scholarly journals Search for non-lactam inhibitors of mtb β-lactamase led to its open shape in apo state: new concept for antibiotic design

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Amin Sagar ◽  
Nazia Haleem ◽  
Yaawar Mir Bashir ◽  
Ashish
Keyword(s):  
Open Shape ◽  
Apo State

TMN X interface testing for pan-European network management

2002 ◽  
Author(s):  
T. Wirkkala ◽  
M. Geymonat ◽  
L. Mathan
Keyword(s):  
Network Management ◽  
European Network ◽  
X Interface

Modelling c-Si/SiN x interface recombination by surface damage

2010 ◽  
Vol 4 (3-4) ◽  
pp. 91-93 ◽  
Author(s):  
Silke Steingrube ◽  
Pietro P. Altermatt ◽  
Jan Schmidt ◽  
Rolf Brendel
Keyword(s):  
Surface Damage ◽  
Interface Recombination ◽  
X Interface

scholarly journals Molecular insights on CALX-CBD12 inter-domain dynamics from MD simulations, RDCs and SAXS

2020 ◽  
Author(s):  
Maximilia F. de Souza Degenhardt ◽  
Phelipe A. M. Vitale ◽  
Layara A. Abiko ◽  
Martin Zacharias ◽  
Michael Sattler ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Md Simulations ◽  
Bound State ◽  
Conformational Ensemble ◽  
Regulation Mechanism ◽  
Multiple Sources ◽  
Intracellular Loop ◽  
Saxs Data ◽  
Structure Information ◽  
Apo State

ABSTRACTNa+/Ca2+ exchangers (NCX) are secondary active transporters that couple the translocation of Na+ with the transport of Ca2+ in the opposite direction. The exchanger is an essential Ca2+ extrusion mechanism in excitable cells. It consists of a transmembrane domain and a large intracellular loop that contains two Ca2+-binding domains, CBD1 and CBD2. The two CBDs are adjacent to each other and form a two-domain Ca2+-sensor called CBD12. Binding of intracellular Ca2+ to CBD12 activates the NCX but inhibits the Na+/Ca2+ exchanger of Drosophila, CALX. NMR spectroscopy and SAXS studies showed that CALX and NCX CBD12 constructs display significant inter-domain flexibility in the Apo state, but assume rigid inter-domain arrangements in the Ca2+-bound state. However, detailed structure information on CBD12 in the Apo state is missing. Structural characterization of proteins formed by two or more domains connected by flexible linkers is notoriously challenging and requires the combination of orthogonal information from multiple sources. As an attempt to characterize the conformational ensemble of CALX-CBD12 in the Apo state, we applied molecular dynamics (MD) simulations, NMR (1H-15N RDCs) and Small-Angle X-Ray Scattering (SAXS) data in a combined modelling strategy that generated atomistic information on the most representative conformations. This joint approach demonstrated that CALX-CBD12 preferentially samples closed conformations, while the wide-open inter-domain arrangement characteristic of the Ca2+-bound state is less frequently sampled. These results are consistent with the view that Ca2+ binding shifts the CBD12 conformational ensemble towards extended conformers, which could be a key step in the Na+/Ca2+ exchangers’ allosteric regulation mechanism. The present strategy, combining MD with NMR and SAXS, provides a powerful approach to select representative structures from ensembles of conformations, which could be applied to other flexible multi-domain systems.SIGNIFICANCEThe conformational ensemble of CALX-CBD12, the main Ca2+-sensor of Drosophila’s Na+/Ca2+ exchanger, was characterized by a combination of MD simulations with SAXS and NMR data using the EOM approach. This analysis showed that this two-domain construct experiences opening-closing motions, providing molecular information about CALX-CBD12 in the Apo state. Ca2+-binding shifts the conformational ensemble towards extended conformers. These findings are consistent with a model according to which Ca2+ modulation of CBD12 plasticity is a key step in the Ca2+-regulation mechanism of the full-length exchanger.

scholarly journals The CytochromecFold Can Be Attained from a Compact Apo State by Occupancy of a Nascent Heme Binding Site

2001 ◽  
Vol 276 (49) ◽  
pp. 45813-45817 ◽  
Author(s):  
Rachel Wain ◽  
Thelma A. Pertinhez ◽  
Esther J. Tomlinson ◽  
Lin Hong ◽  
Christopher M. Dobson ◽  
...  
Keyword(s):  
Binding Site ◽  
Heme Binding ◽  
Apo State

Ultrathin TiO x Interface‐Mediated ZnO‐Nanowire Memristive Devices Emulating Synaptic Behaviors

2019 ◽  
Vol 5 (6) ◽  
pp. 1900142 ◽  
Author(s):  
Ming Xiao ◽  
Travis Yeow ◽  
Viet Huong Nguyen ◽  
David Muñoz‐Rojas ◽  
Kevin P. Musselman ◽  
...  
Keyword(s):  
Zno Nanowire ◽  
X Interface
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