Structural and Thermodynamic Investigations on the Aggregation and Folding of Acylphosphatase by Molecular Dynamics Simulations and Solvation Free Energy Analysis

2011 ◽  
Vol 133 (18) ◽  
pp. 7075-7083 ◽  
Author(s):  
Song-Ho Chong ◽  
Chewook Lee ◽  
Guipeun Kang ◽  
Mirae Park ◽  
Sihyun Ham
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Energy Analysis ◽  
Solvation Free Energy ◽  
Dynamics Simulations ◽  
Free Energy Analysis

Molecular dynamics simulations and binding free energy analysis of DNA minor groove complexes of curcumin

2011 ◽  
Vol 17 (11) ◽  
pp. 2805-2816 ◽  
Author(s):  
Mathew Varghese Koonammackal ◽  
Unnikrishnan Viswambharan Nair Nellipparambil ◽  
Chellappanpillai Sudarsanakumar
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Energy Analysis ◽  
Binding Free Energy ◽  
Minor Groove ◽  
Dna Minor Groove ◽  
Dynamics Simulations ◽  
Free Energy Analysis

Molecular dynamics simulations studies and free energy analysis on inhibitors of MDM2–p53 interaction

2013 ◽  
Vol 46 ◽  
pp. 132-139 ◽  
Author(s):  
Rui-Juan Niu ◽  
Qing-Chuan Zheng ◽  
Ji-Long Zhang ◽  
Hong-Xing Zhang
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Energy Analysis ◽  
Dynamics Simulations ◽  
Free Energy Analysis

scholarly journals Dynamics and Thermodynamics of Transthyretin Association from Molecular Dynamics Simulations

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Cedrix J. Dongmo Foumthuim ◽  
Alessandra Corazza ◽  
Rodolfo Berni ◽  
Gennaro Esposito ◽  
Federico Fogolari
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Energy Analysis ◽  
Wild Type ◽  
Triple Mutant ◽  
Energy Functions ◽  
Dimer Interface ◽  
Dynamics Simulations ◽  
Free Energy Analysis ◽  
Effective Energy Functions

Molecular dynamics simulations are used in this work to probe the structural stability and the dynamics of engineered mutants of transthyretin (TTR), i.e., the double mutant F87M/L110M (MT-TTR) and the triple mutant F87M/L110M/S117E (3M-TTR), in relation to wild-type. Free energy analysis from end-point simulations and statistical effective energy functions are used to analyze trajectories, revealing that mutations do not have major impact on protein structure but rather on protein association, shifting the equilibria towards dissociated species. The result is confirmed by the analysis of 3M-TTR which shows dissociation within the first 10 ns of the simulation, indicating that contacts are lost at the dimer-dimer interface, whereas dimers (formed by monomers which pair to form two extended β-sheets) appear fairly stable. Overall the simulations provide a detailed view of the dynamics and thermodynamics of wild-type and mutant transthyretins and a rationale of the observed effects.

Molecular Basis of Glucose Transport Mechanism in Plants

2019 ◽  
Author(s):  
Balaji Selvam ◽  
Ya-Chi Yu ◽  
Liqing Chen ◽  
Diwakar Shukla
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Conformational Changes ◽  
Transport Mechanism ◽  
Conformational Dynamics ◽  
Site Directed Mutagenesis ◽  
Free Energy Barrier ◽  
Transport Cycle ◽  
Dynamics Simulations

<p>The SWEET family belongs to a class of transporters in plants that undergoes large conformational changes to facilitate transport of sugar molecules across the cell membrane. However, the structures of their functionally relevant conformational states in the transport cycle have not been reported. In this study, we have characterized the conformational dynamics and complete transport cycle of glucose in OsSWEET2b transporter using extensive molecular dynamics simulations. Using Markov state models, we estimated the free energy barrier associated with different states as well as 1 for the glucose the transport mechanism. SWEETs undergoes structural transition to outward-facing (OF), Occluded (OC) and inward-facing (IF) and strongly support alternate access transport mechanism. The glucose diffuses freely from outside to inside the cell without causing major conformational changes which means that the conformations of glucose unbound and bound snapshots are exactly same for OF, OC and IF states. We identified a network of hydrophobic core residues at the center of the transporter that restricts the glucose entry to the cytoplasmic side and act as an intracellular hydrophobic gate. The mechanistic predictions from molecular dynamics simulations are validated using site-directed mutagenesis experiments. Our simulation also revealed hourglass like intermediate states making the pore radius narrower at the center. This work provides new fundamental insights into how substrate-transporter interactions actively change the free energy landscape of the transport cycle to facilitate enhanced transport activity.</p>

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