Definition and testing of the GROMOS force-field versions 54A7 and 54B7

Schmid, Nathan; Eichenberger, Andreas P.; Choutko, Alexandra; Riniker, Sereina; Winger, Moritz; Mark, Alan E.; Gunsteren, Wilfred F. van

doi:10.1007/s00249-011-0700-9

Cited by 2,159 publications

(1,904 citation statements)

References 37 publications

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“…The simulation box, including water and ions to neutralize the system, was 13 × 13 × 16 nm. Energy minimization, equilibration protocols and production runs were carried out with GROMACS 4.5.5 (Berendsen et al , 1995; Hess et al , 2008), using the ff54a7 version of the GROMOS 96 force field (Poger & Mark, 2010; Poger et al , 2010; Schmid et al , 2011). …”

Section: Methodsmentioning

confidence: 99%

Structural basis for antibacterial peptide self‐immunity by the bacterial ABC transporter McjD

et al. 2017

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Certain pathogenic bacteria produce and release toxic peptides to ensure either nutrient availability or evasion from the immune system. These peptides are also toxic to the producing bacteria that utilize dedicated ABC transporters to provide self‐immunity. The ABC transporter McjD exports the antibacterial peptide MccJ25 in Escherichia coli. Our previously determined McjD structure provided some mechanistic insights into antibacterial peptide efflux. In this study, we have determined its structure in a novel conformation, apo inward‐occluded and a new nucleotide‐bound state, high‐energy outward‐occluded intermediate state, with a defined ligand binding cavity. Predictive cysteine cross‐linking in E. coli membranes and PELDOR measurements along the transport cycle indicate that McjD does not undergo major conformational changes as previously proposed for multi‐drug ABC exporters. Combined with transport assays and molecular dynamics simulations, we propose a novel mechanism for toxic peptide ABC exporters that only requires the transient opening of the cavity for release of the peptide. We propose that shielding of the cavity ensures that the transporter is available to export the newly synthesized peptides, preventing toxic‐level build‐up.

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Section: Methodsmentioning

confidence: 99%

Structural basis for antibacterial peptide self‐immunity by the bacterial ABC transporter McjD

et al. 2017

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“…Long-range corrections of the electrostatic interactions beyond the cut-off were calculated using the Particle Mesh Ewald (PME) method (Essmann et al 1995). The united atom option of GROMOS 54a7 force field (Huang et al 2011;Schmid et al 2011;) was used to calculate the intermolecular and intramolecular interactions for all systems. The DMPC topology was constructed from the Automated Topology Builder (ATB) and repository (Malde et al 2011).…”

Section: Computational Details Of the Simulationsmentioning

confidence: 99%

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

et al. 2017

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Emodin is one of the most abundant anthraquinone derivatives found in nature. It is the active principle of some traditional herbal medicines with known biological activities. In this work, we combined experimental and theoretical studies to reveal information about location, orientation, interaction and perturbing effects of Emodin on lipid bilayers, where we have taken into account the neutral form of the Emodin (EMH) and its anionic/deprotonated form (EM − ). Using both UV/Visible spectrophotometric techniques and molecular dynamics (MD) simulations, we showed that both EMH and EM − are located in a lipid membrane. Additionally, using MD simulations, we revealed that both forms of Emodin are very close to glycerol groups of the lipid molecules, with the EMH inserted more deeply into the bilayer and more disoriented relative to the normal of the membrane when compared with the EM − , which is more exposed to interfacial water. Analysis of several structural properties of acyl chains of the lipids in a hydrated pure DMPC bilayer and in the presence of Emodin revealed that both EMH and EM − affect the lipid bilayer, resulting in a remarkable disorder of the bilayer in the vicinity of the Emodin. However, the disorder caused by EMH is weaker than that caused by EM − . Our results suggest that these disorders caused by Emodin might lead to distinct effects on lipid bilayers including its disruption which are reported in the literature.

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“…The remaining histidines residues were kept at a protonation state with charge 0. Simulations were carried out using the GROMOS force field force parameter set 54A7 [48][49][50] in conjunction with the software package GROMACS v.4.5.4 double precision. 51,52 Atomic parameters for DDT and GSH were taken from GROMOS force field force parameter set 54A7.…”

Section: Molecular Docking Of Ddt To Aggste Variantsmentioning

confidence: 99%

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

Pontes¹,

Maia²,

Lima³

et al. 2016

Journal of the Brazilian Chemical Society

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Glutathione S-transferases (GSTs) are enzymes capable of metabolizing cytotoxic compounds. The enzyme AgGSTE2, member of epsilon class GSTs (GSTE), is the most important GST conferring resistance to dichloro-diphenyl-trichloroethane (DDT) in Anopheles gambiae. We have investigated the conformational dynamics of three GSTE variants (GSTE2, GSTE2-I114T/F120L, GSTE5) from A. gambiae. Large-scale motions of helices H2 and H4 and conformational transition of the C-terminal governs the opening of the G-site and is expected to affect substrate binding and product release. This structural rearrangement places Glu116 (Glu120 in GSTE5) close of the thiol group of the tripeptide glutathione (GSH) cofactor, making this residue a candidate to act as a base in the activation of DDT. The structural rearrangement is noticeable for AgGSTE2-F120L, which has been shown to confer increased DDT-resistance. The other variants exhibit a more subtle rearrangement. These findings corroborate the hypothesis that the increase of the conformational dynamics of GST Epsilon class isoforms from A. gambiae promotes higher DDTase activity.Keywords: molecular dynamics simulation, evolutional constraint, positive and negative selection, metabolic resistance, malaria vector IntroductionGlutathione transferases (EC 2.5.1.18) are highly promiscuous proteins where broad functional promiscuity co-exists with highly conserved structural fold. Glutathione S-transferases (GSTs) constitute a large family of cytosolic and membrane-bound proteins that catalyze the nucleophilic addition of the tripeptide glutathione (GSH) to a variety of electrophilic toxins and drugs (xenobiotics), leading to their excretion. 1,2 Lately, several other activities have also been associated with GSTs, including steroid and leukotriene biosynthesis, peroxide degradation, doublebond cis-trans isomerization, dehydroascorbate reduction, Michael addition, and noncatalytic ligand binding and transport activity. 3 These polymorphic enzymes belong to supergene families whose members are generated by punctual mutations, gene duplication and alternative splicing. 4 The GST family is subdivided into several classes accordingly to its occurrence in different taxa.The number of isoforms per class varies widely, ranging from one to forty. 4 A single GST isoform is capable of conjugating glutathione to several hydrophobic substrates. Such promiscuity when coupled with the large number of isozymes generates a large range of potential substrates.Insects exhibit at least six classes of GSTs (Sigma, Omega, Theta, Zeta, Delta and Epsilon) with the first four classes present in almost all living organisms. 4,5 The Epsilon and Delta classes are arthropod specific and some members of these classes have been associated to insecticide resistance in culicid vectors. 5,6 The metabolism of toxic compounds in insects is conducted by a series of enzymes from different phases and GSTs act in phase II. GSTs metabolize these compounds in two ways: one has been cited above (through GSH conjugation) and the oth...

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Definition and testing of the GROMOS force-field versions 54A7 and 54B7

Cited by 2,159 publications

References 37 publications

Structural basis for antibacterial peptide self‐immunity by the bacterial ABC transporter McjD

Structural basis for antibacterial peptide self‐immunity by the bacterial ABC transporter McjD

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

The Role of the Conformational Dynamics of Glutathione S-Transferase Epsilon Class on Insecticide Resistance inAnopheles gambiae

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