CHARMM-GUI<i>Membrane Builder</i>toward realistic biological membrane simulations

Wu, Emilia L.; Cheng, Xi; Jo, Sunhwan; Rui, Huan; Song, Kevin; Dávila-Contreras, Eder M.; Qi, Yue; Lee, Jumin; Monje-Galvan, Viviana; Venable, Richard M.; Klauda, Jeffery B.; Im, Wonpil

doi:10.1002/jcc.23702

Cited by 1,911 publications

(1,609 citation statements)

References 67 publications

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“…Initial peptide structures were built with CHARMM 55,56 in extended conformations. The phospholipid bilayers with a single copy of peptide in aqueous phase were created by using CHARMM-GUI [57][58][59] and all molecular dynamics simulations were conducted with GROMACS 4.5.4 or 4.5.6. 60 The bilayer systems contained the following molecules: 50 (2 × 25) 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) molecules, one peptide, eight chloride, and eight sodium ions and TIP3P water.…”

Section: Computationalmentioning

confidence: 99%

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Lee

Kuczera

Middaugh

et al. 2016

The Journal of Chemical Physics

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The time-resolved parallel artificial membrane permeability assay with fluorescence detection and comprehensive computer simulations are used to study the passive permeation of three aromatic dipeptides—N-acetyl-phenylalanineamide (NAFA), N-acetyltyrosineamide (NAYA), and N-acetyl-tryptophanamide (NATA) through a 1,2-dioleoyl-sn-glycero-3-phospocholine (DOPC) lipid bilayer. Measured permeation times and permeability coefficients show fastest translocation for NAFA, slowest for NAYA, and intermediate for NATA under physiological temperature and pH. Computationally, we perform umbrella sampling simulations to model the structure, dynamics, and interactions of the peptides as a function of z, the distance from lipid bilayer. The calculated profiles of the potential of mean force show two strong effects—preferential binding of each of the three peptides to the lipid interface and large free energy barriers in the membrane center. We use several approaches to calculate the position-dependent translational diffusion coefficients D(z), including one based on numerical solution the Smoluchowski equation. Surprisingly, computed D(z) values change very little with reaction coordinate and are also quite similar for the three peptides studied. In contrast, calculated values of sidechain rotational correlation times τrot(z) show extremely large changes with peptide membrane insertion—values become 100 times larger in the headgroup region and 10 times larger at interface and in membrane center, relative to solution. The peptides’ conformational freedom becomes systematically more restricted as they enter the membrane, sampling α and β and C7eq basins in solution, α and C7eq at the interface, and C7eq only in the center. Residual waters of solvation remain around the peptides even in the membrane center. Overall, our study provides an improved microscopic understanding of passive peptide permeation through membranes, especially on the sensitivity of rotational diffusion to position relative to the bilayer.

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Section: Computationalmentioning

confidence: 99%

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Lee

Kuczera

Middaugh

et al. 2016

The Journal of Chemical Physics

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“…We modeled homogeneous lipid A bilayers for 21 different lipid A types (Table 1) following the CHARMM-GUI Membrane Builder step-by-step protocol (39)(40)(41). The force-field parameters for each lipid A were assigned from the CHARMM36 force field for LPS (42), lipids (43), carbohydrates (44)(45)(46), and proteins (47).…”

Section: Simulation Systems and Protocolsmentioning

confidence: 99%

Bilayer Properties of Lipid A from Various Gram-Negative Bacteria

Kim

Patel

Park

et al. 2016

Biophysical Journal

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130

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Lipid A is the lipid anchor of a lipopolysaccharide in the outer leaflet of the outer membrane of Gram-negative bacteria. In general, lipid A consists of two phosphorylated N-acetyl glucosamine and several acyl chains that are directly linked to the two sugars. Depending on the bacterial species and environments, the acyl chain number and length vary, and lipid A can be chemically modified with phosphoethanolamine, aminoarabinose, or glycine residues, which are key to bacterial pathogenesis. In this work, homogeneous lipid bilayers of 21 distinct lipid A types from 12 bacterial species are modeled and simulated to investigate the differences and similarities of their membrane properties. In addition, different neutralizing ion types (Ca 2þ , K þ , and Na þ ) are considered to examine the ion's influence on the membrane properties. The trajectory analysis shows that (1) the area per lipid is mostly correlated to the acyl chain number, and the area per lipid increases as a function of the acyl chain number; (2) the hydrophobic thickness is mainly determined by the average acyl chain length with slight dependence on the acyl chain number, and the hydrophobic thickness generally increases with the average acyl chain length; (3) a good correlation is observed among the area per lipid, hydrophobic thickness, and acyl chain order; and (4) although the influence of neutralizing ion types on the area per lipid and hydrophobic thickness is minimal, Ca 2þ stays longer on the membrane surface than K þ or Na þ , consequently leading to lower lateral diffusion and a higher compressibility modulus, which agrees well with available experiments.

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“…The structural models were inserted into lipids using the CHARMM-GUI web interface [18,19]. Production runs at 310 K were performed after energy minimization and equilibration steps using GROMACS with CHARMM36 force field [20,21].…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

Molecular dynamics of the cryo-EM CFTR structure

Tordai

Leveles

Hegedüs

2017

Biochemical and Biophysical Research Communications

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Cystic fibrosis (CF), a lethal monogenic disease, is caused by mutant variants of the CF transmembrane conductance regulator (CFTR). Recent advances in single molecule cryo-EM methods enabled structural determination of full-length human and zebrafish CFTR, achieving an important milestone for CF drug development. To relate these structures to the gating cycle, we examined its dynamic features using molecular dynamics simulations. Our results show that the nucleotide binding domains (NBDs) in this bottom-open apo conformation exhibit motions related to dimerization and the bottom-closed apo CFTR model indicates opening of NBDs in contrast to transporters. These observations help in understanding the properties of CFTR chloride channel distinct from transporters and in proper interpretation of available structural information on this ABC protein.

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CHARMM-GUIMembrane Buildertoward realistic biological membrane simulations

Cited by 1,911 publications

References 67 publications

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

Bilayer Properties of Lipid A from Various Gram-Negative Bacteria

Molecular dynamics of the cryo-EM CFTR structure

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