Effect of External Electric Field on Substrate Transport of a Secondary Active Transporter

Zhang, Jilong; Zheng, Qing‐Chuan; Yu, Lu; Li, Zhengqiang; Zhang, Hongxing

doi:10.1021/acs.jcim.6b00212

Cited by 5 publications

(3 citation statements)

References 65 publications

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“…A force constant of harmonic restraint and a pulling velocity were set to 0.2 kcal mol –1 Å –2 and 5 Å ns –1 , respectively. Through several tests, combined with our previous works, − we confirmed that the two parameters are suitable for the present simulation about the unbinding of KAR 1 . While keeping the alpha-carbon (Cα) atoms of three residues (Ser31, Leu77, and Ala102) fixed, external steering force was exerted on the center of mass (COM) of the ligand KAR 1 along the direction determined by the vector from the CG atom (atom name in the force field file) of Leu77 to the O10 atom of the ligand.…”

Section: Computational Detailssupporting

confidence: 78%

“…Until now, however, no simulation work on the KAI2–KAR binding has been reported. In the present research, the detailed binding process of KAR 1 to its receptor protein KAI2, together with the related binding energetics, was investigated by the proper integration of several MD simulation techniques which have been proven to be powerful in addressing similar protein–ligand binding issues. − On the basis of steered molecular dynamics (SMD) simulations, the adaptive biasing force (ABF) method was used to obtain the potential of mean force (PMF) of the binding process and reveal the conformational changes of the protein and the ligand. Our simulation results present a dynamic binding view of KAR 1 to KAI2 and will be helpful for the more penetrating understanding of the physiological function of the KAR signal molecule family and their receptor.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MD Simulation Investigation on the Binding Process of Smoke-Derived Germination Stimulants to Its Receptor

Liu

Zhang

et al. 2019

J. Chem. Inf. Model.

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Karrikins (KARs) are a class of smoke-derived seed germination stimulants with great significance in both agriculture and plant biology. By means of direct binding to the receptor protein KAI2, the compounds can initiate the KAR signal transduction pathway, hence triggering germination of the dormant seeds in the soil. In the research, several molecular dynamics (MD) simulation techniques were properly integrated to investigate the binding process of KAR1 to KAI2 and reveal the details of the whole binding event. The calculated binding free energy, −7.00 kcal/mol, is in good agreement with the experimental measurement, −6.83 kcal/mol. The obtained PMF profile indicates the existence of three intermediate states in the binding process. The analysis of the simulation trajectories demonstrates that, in the intermediate structures, KAR1 is stabilized by some hydrophobic residues (Phe26, Phe134, Leu142, Trp153, Phe157, Leu160, Phe194), along with several bridging water molecules, and meanwhile, the significant shifting occurs in the local conformation of the protein as the ligand’s binding. A series of the residues (Gln141–Phe157) on the so-called “cap domain” are proposed to be responsible for capturing the ligand at the initial stage of the binding. Besides, the changes of the ligand’s poses are also quantitatively characterized by the proper choice of the coordinate system. Our work will contribute to the more penetrating understanding of the ligand binding process and the receptor affinity difference between several members in the KAR family and help design new, more effective germination stimulants.

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Section: Computational Detailssupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

MD Simulation Investigation on the Binding Process of Smoke-Derived Germination Stimulants to Its Receptor

Liu

Zhang

et al. 2019

J. Chem. Inf. Model.

Self Cite

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“…Recently, Cappet et al demonstrated a high level of predictability to calculate binding free energy using homology models with very low identity (∼22%) similar to levels found between hNIS, hSMCT1 and the vSGLT template. Moreover, it should be noted that the ABF method has been applied successfully in evaluations of substrate transport in transmembrane proteins, , whereas the Drude polarizable force field has shown superior accuracy in describing ion–protein interactions . Iodide has the highest polarizability among common monatomic ions and polarizability is particularly important in describing interactions between ions and tryptophan, a residue located in the predicted iodide binding pockets.…”

Section: Discussionmentioning

confidence: 99%

Iodide Binding in Sodium-Coupled Cotransporters

Vergara-Jaque

Fong

Comer

2017

J. Chem. Inf. Model.

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Several apical iodide translocation pathways have been proposed for iodide efflux out of thyroid follicular cells, including a pathway mediated by the sodium-coupled monocarboxylate transporter 1 (SMCT1), which remains controversial. Herein, we evaluate structural and functional similarities between SMCT1 and the well-studied sodium-iodide symporter (NIS) that mediates the first step of iodide entry into the thyroid. Free-energy calculations using a force field with electronic polarizability verify the presence of a conserved iodide-binding pocket between the TM2, TM3, and TM7 segments in hNIS, where iodide is coordinated by Phe67, Gln72, Cys91, and Gln94. We demonstrate the mutation of residue Gly93 of hNIS to a larger amino acid expels the side chain of a critical tryptophan residue (Trp255) into the interior of the binding pocket, partially occluding the iodide binding site and reducing iodide affinity, which is consistent with previous reports associating mutation of this residue with iodide uptake deficiency and hypothyroidism. Furthermore, we find that the position of Trp255 in this hNIS mutant mirrors that of Trp253 in wild-type hSMCT1, where a threonine (Thr91) occupies the position homologous to that occupied by glycine in wild-type hNIS (Gly93). Correspondingly, mutation of Thr91 to glycine in hSMCT1 makes the pocket structure more like that of wild-type hNIS, increasing its iodide affinity. These results suggest that wild-type hSMCT1 in the inward-facing conformation may bind iodide only very weakly, which may have implications for its ability to transport iodide.

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Membrane Transport: Energetics and Overview

Henderson¹

2018

Encyclopedia of Biophysics

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Effect of External Electric Field on Substrate Transport of a Secondary Active Transporter

Cited by 5 publications

References 65 publications

MD Simulation Investigation on the Binding Process of Smoke-Derived Germination Stimulants to Its Receptor

MD Simulation Investigation on the Binding Process of Smoke-Derived Germination Stimulants to Its Receptor

Iodide Binding in Sodium-Coupled Cotransporters

Membrane Transport: Energetics and Overview

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