Binding of 5‘-GMP to the GluR2 AMPA Receptor:  Insight from Targeted Molecular Dynamics Simulations†

Biochemistry ◽  
2005 ◽  
Vol 44 (44) ◽  
pp. 14470-14476 ◽  
Author(s):  
Jesús Mendieta ◽  
Federico Gago ◽  
Galo Ramírez
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Ampa Receptor ◽  
Targeted Molecular Dynamics ◽  
Dynamics Simulations

scholarly journals Estimation of Protein–Ligand Unbinding Kinetics Using Non-Equilibrium Targeted Molecular Dynamics Simulations

2019 ◽  
Vol 59 (12) ◽  
pp. 5135-5147 ◽  
Author(s):  
Steffen Wolf ◽  
Marta Amaral ◽  
Maryse Lowinski ◽  
Francois Vallée ◽  
Djordje Musil ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Targeted Molecular Dynamics ◽  
Dynamics Simulations ◽  
Non Equilibrium

Targeted Molecular Dynamics Simulations of Protein Unfolding

2000 ◽  
Vol 104 (18) ◽  
pp. 4511-4518 ◽  
Author(s):  
Philippe Ferrara ◽  
Joannis Apostolakis ◽  
Amedeo Caflisch
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Protein Unfolding ◽  
Targeted Molecular Dynamics ◽  
Dynamics Simulations

scholarly journals Targeted Molecular Dynamics Simulations Suggest Direct Ligand Competition as a Plausible Efflux Inhibition Mechanism in the Multidrug Resistance Pump AcrB

2018 ◽  
Author(s):  
Lande Silva ◽  
Pedro Eduardo Almeida da Silva ◽  
Karina S. Machado ◽  
Nelson Dutra ◽  
Terry P. Lybrand
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Efflux Pump ◽  
Outer Part ◽  
Inhibition Mechanism ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Targeted Molecular Dynamics ◽  
Calculation Results ◽  
Dynamics Simulations

AbstractWe report computer simulation results using the Targeted Molecular Dynamics technique to explore possible transport mechanisms in the multidrug efflux pump AcrB for two substrates, ethidium bromide and a tetrahydropyridine derivative. These studies revealed structural elements, including specific α-helices, β-strands and flexible loops that define a physically plausible pathway for substrates to the extracellular environment. These calculation results can be used to plan future biophysical experiments and may suggest interesting drug design possibilities to address drug resistance due to AcrB function.ImportanceAddressing the issue of antimicrobial resistance mediated by efflux, this study presents possible binding sites and structures in the AcrB MDR pump that could be molecular targets for drugs. Targeted molecular dynamics simulations suggested that these sites and structures seem vital for a successful efflux. The AcrB is proposed to be divided into three distinct zones, with loops, sheets and helices mediating the passage of molecules from one zone to another. We also described possible capture sites on the outer part of the protein and access ways to its interior. Finally, we proposed that ligand competition for same pathways could be thought as an efflux inhibitory mechanism, thus assisting to conceive new ways of designing efflux pump inhibitors.

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