scholarly journals How antiporters exchange substrates across the cell membrane? An atomic-level description of the complete exchange cycle in NarK

2020 ◽  
Author(s):  
Jiangyan Feng ◽  
Balaji Selvam ◽  
Diwakar Shukla
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Conformational Transition ◽  
Atomic Level ◽  
Major Facilitator Superfamily ◽  
Electrostatic Repulsion ◽  
State Dependent ◽  
Complete Exchange ◽  
Dynamics Simulations ◽  
Major Facilitator

Major facilitator superfamily (MFS) proteins operate via three different mechanisms: uniport, symport, and antiport. Despite extensive investigations, molecular understanding of antiporters is less advanced than other transporters due to the complex coupling between two substrates and the lack of distinct structures. We employ extensive (~300 μs)all-atom molecular dynamics simulations to dissect the complete substrate exchange cycle of the bacterial NO3−/NO2− antiporter, NarK. We show that paired basic residues in the binding site prevent the closure of unbound protein and ensure the exchange of two substrates. Conformational transition only occurs in the presence of substrate, which weakens the electrostatic repulsion and stabilizes the transporter by ∼1.5 kcal/mol. Furthermore, we propose a state-dependent substrate exchange model, in which the relative spacing between the paired basic residues determines whether NO3− and NO2− bind simultaneously or sequentially. Overall, this work presents a general working model for the antiport mechanism within MFS family.

How calcium ion binding induces the conformational transition of the calmodulin N-terminal domain—an atomic level characterization

2019 ◽  
Vol 21 (36) ◽  
pp. 19795-19804 ◽  
Author(s):  
Likun Zhao ◽  
Luhua Lai ◽  
Zhuqing Zhang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Calcium Ion ◽  
Conformational Transition ◽  
Atomic Level ◽  
Ion Binding ◽  
Terminal Domain ◽  
Calcium Ion Binding ◽  
Dynamics Simulations ◽  
Conformation Transition

The Ca2+ binding and triggering conformation transition of nCaM were detected in unbiased molecular dynamics simulations.

scholarly journals Molecular dynamics simulations and experimental studies reveal differential permeability of withaferin-A and withanone across the model cell membrane

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Renu Wadhwa ◽  
Neetu Singh Yadav ◽  
Shashank P. Katiyar ◽  
Tomoko Yaguchi ◽  
Chohee Lee ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Molecular Dynamics Simulations ◽  
Experimental Studies ◽  
Bilayer Membrane ◽  
Withaferin A ◽  
Head Group ◽  
Polar Head Group ◽  
Natural Drugs ◽  
Dynamics Simulations

AbstractPoor bioavailability due to the inability to cross the cell membrane is one of the major reasons for the failure of a drug in clinical trials. We have used molecular dynamics simulations to predict the membrane permeability of natural drugs—withanolides (withaferin-A and withanone) that have similar structures but remarkably differ in their cytotoxicity. We found that whereas withaferin-A, could proficiently transverse through the model membrane, withanone showed weak permeability. The free energy profiles for the interaction of withanolides with the model bilayer membrane revealed that whereas the polar head group of the membrane caused high resistance for the passage of withanone, the interior of the membrane behaves similarly for both withanolides. The solvation analysis further revealed that the high solvation of terminal O5 oxygen of withaferin-A was the major driving force for its high permeability; it interacted with the phosphate group of the membrane that led to its smooth passage across the bilayer. The computational predictions were tested by raising and recruiting unique antibodies that react to withaferin-A and withanone. The time-lapsed analyses of control and treated cells demonstrated higher permeation of withaferin-A as compared to withanone. The concurrence between the computation and experimental results thus re-emphasised the use of computational methods for predicting permeability and hence bioavailability of natural drug compounds in the drug development process.

UNDERSTANDING DIFFERENT LCST LEVELS OF POLY(N-ALKYLACRYLAMIDE)S BY MOLECULAR DYNAMICS SIMULATIONS AND QUANTUM MECHANICS CALCULATIONS

2011 ◽  
Vol 10 (03) ◽  
pp. 359-370 ◽  
Author(s):  
JUAN PANG ◽  
HU YANG ◽  
JING MA ◽  
RONGSHI CHENG
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Aqueous Solutions ◽  
Molecular Dynamics Simulations ◽  
Steric Effect ◽  
Conformational Transition ◽  
Methyl Group ◽  
Branched Chain ◽  
Dynamics Simulations ◽  
Different Levels

Poly(N-alkylacrylamide) is a group of thermo-sensitive polymers that include poly (N-isopropylacrylamide), poly(N-n-propylacrylamide), poly(N-isopropylmethacryl-amide), and so on. The polymers exhibit different levels of lower critical solution temperatures (LCST) in aqueous solutions. In this article, their monomers and oligomers with 10 repeating units are selected, respectively, to demonstrate the cause of different LCST levels of the polymers in aqueous solutions using molecular dynamics simulations and quantum mechanics calculations. The monomers have functional groups of different steric volume that greatly affect the conformational transition of chains and LCST levels of the polymers. A branched chain of N-propyl group in N-isopropylacrylamide and an additional methyl group at α-carbon in N-isopropylmethacrylamide both increase the steric effect, making it more difficult for monomers to draw closer and resulting in higher LCST levels of the polymers. In addition, the simulated results from their corresponding oligomers exhibit the similar trend to those from the monomers.

scholarly journals Exploring Dynamics and Structure of Biomolecules, Cryoprotectants, and Water Using Molecular Dynamics Simulations: Implications for Biostabilization and Biopreservation

2019 ◽  
Vol 21 (1) ◽  
pp. 1-31 ◽  
Author(s):  
Lindong Weng ◽  
Shannon L. Stott ◽  
Mehmet Toner
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Molecular Motion ◽  
State Of The Art ◽  
Level Structure ◽  
Cost Effective ◽  
Atomic Level ◽  
Computational Research ◽  
Dynamics Simulations ◽  
Biological Entities

Successful stabilization and preservation of biological materials often utilize low temperatures and dehydration to arrest molecular motion. Cryoprotectants are routinely employed to help the biological entities survive the physicochemical and mechanical stresses induced by cold or dryness. Molecular interactions between biomolecules, cryoprotectants, and water fundamentally determine the outcomes of preservation. The optimization of assays using the empirical approach is often limited in structural and temporal resolution, whereas classical molecular dynamics simulations can provide a cost-effective glimpse into the atomic-level structure and interaction of individual molecules that dictate macroscopic behavior. Computational research on biomolecules, cryoprotectants, and water has provided invaluable insights into the development of new cryoprotectants and the optimization of preservation methods. We describe the rapidly evolving state of the art of molecular simulations of these complex systems, summarize the molecular-scale protective and stabilizing mechanisms, and discuss the challenges that motivate continued innovation in this field.

scholarly journals Structure and Dynamics of Glycosphingolipids in Lipid Bilayers: Insights from Molecular Dynamics Simulations

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ronak Y. Patel ◽  
Petety V. Balaji
Keyword(s):  
Molecular Dynamics ◽  
Lipid Bilayers ◽  
Membrane Structure ◽  
Lipid Membrane ◽  
Biological Membranes ◽  
Md Simulations ◽  
Atomic Level ◽  
Structure And Dynamics ◽  
Hydrogen Bonding Interactions ◽  
Dynamics Simulations

Glycolipids are important constituents of biological membranes, and understanding their structure and dynamics in lipid bilayers provides insights into their physiological and pathological roles. Experimental techniques have provided details into their behavior at model and biological membranes; however, computer simulations are needed to gain atomic level insights. This paper summarizes the insights obtained from MD simulations into the conformational and orientational dynamics of glycosphingolipids and their exposure, hydration, and hydrogen-bonding interactions in membrane environment. The organization of glycosphingolipids in raft-like membranes and their modulation of lipid membrane structure are also reviewed.

Sign in / Sign up

Export Citation Format

Share Document