Molecular dynamics simulation of the transmembrane subunit of BtuCD in the lipid bilayer

Sun, Tingguang; Liu, Ming; Chen, Weizu; Wang, Cunxin

doi:10.1007/s11427-010-0103-7

Cited by 10 publications

(6 citation statements)

References 46 publications

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“…87 Additionally, eukaryotic membranes are richer in polyunsaturated lipids than saturated ones, a fact by which the POPC lipid is more adequate for the simulation of such transporters, in agreement with a previous study on a similar framework. 88 In order to assess the importance of the linker in the stability of the whole structure, the corresponding secondary structure was built on the basis of secondary structure prediction programs. A more exhaustive characterization was also made at PredictProtein.org, 89 which confirmed that 87.72% of the residues were exposed and the probability for the occurrence of structures as α-helix or β-sheets was only 10.53%.…”

Section: ■ Resultsmentioning

confidence: 99%

Insights on P-Glycoprotein’s Efflux Mechanism Obtained by Molecular Dynamics Simulations

Ferreira

Santos

2012

J. Chem. Theory Comput.

114

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P-Glycoprotein (P-gp) is often involved in multidrug resistance (MDR) to the pharmacological action of a wide number of anticancer agents. In this article, a series of molecular dynamics simulations of murine's P-gp were developed, elucidating the importance of the lipid membrane and linker sequence in the protein structure stability. The behavior of several molecules inside the drug-binding pocket revealed a striking difference between substrates or modulators, and motion patterns were identified that could be correlated with conformational alterations due to substrate binding, corresponding to the initial step in the efflux mechanism. Only one "entrance gate" to the drug-binding pocket was found and, in the presence of a substrate, leads to changes in the motion patterns of the transporter into an efflux-like movement.

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Section: ■ Resultsmentioning

confidence: 99%

Insights on P-Glycoprotein’s Efflux Mechanism Obtained by Molecular Dynamics Simulations

Ferreira

Santos

2012

J. Chem. Theory Comput.

114

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“…1 B). This approach is similar to that used in a previous MD study of the Sav1866 homolog, the MsbA lipid A transporter (29), in which only the predicted membranespanning segments were simulated, as well as in many studies in which isolated TMD (30) or NBD (31)(32)(33)(34)(35)(36)(37)(38)(39) domains of ABC transporters were simulated.…”

Section: Resultsmentioning

confidence: 99%

Molecular-Dynamics Simulations of the ATP/apo State of a Multidrug ATP-Binding Cassette Transporter Provide a Structural and Mechanistic Basis for the Asymmetric Occluded State

Jones

George

2011

Biophysical Journal

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ATP-binding cassette transporters use the energy of ATP hydrolysis to transport substrates across cellular membranes. They have two transmembrane domains and two cytosolic nucleotide-binding domains. Biochemical studies have characterized an occluded state of the transporter in which nucleotide is tenaciously bound in one active site, whereas the opposite active site is empty or binds nucleotide loosely. Here, we report molecular-dynamics simulations of the bacterial multidrug ATP-binding cassette transporter Sav1866. In two simulations of the ATP/apo state, the empty site opened substantially by way of rotation of the nucleotide-binding domain (NBD) core subdomain, whereas the ATP-bound site remained occluded and intact. We correlate our findings with elastic network and molecular-dynamics simulation analyses of the Sav1866 NBD monomer, and with existing experimental data, to argue that the observed transition is physiological, and that the final structure observed in the ATP/apo simulations corresponds to the tight/loose state of the NBD dimer characterized experimentally.

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“…The periodic boundary conditions were applied in all the three dimensions. Time step used was 2 fs [25] using Leap Frog Algorithm [26] and Berendsen scheme [27] was used for temperature control using a coupling time constant: τ t of 0.1 ps and a reference temperature T 0 of 300 K. LINCS algorithm [28] was used to restrict all bonds to their equilibrium lengths and the centre of mass motion of the system was removed at every step to maintain T 0 . Pressure was controlled using weak coupling with a time constant of 0.5 ps and a reference pressure of 1 Bar.…”

Section: Molecular Dynamic (Md) Simulationsmentioning

confidence: 99%

A Unique Conformational Behaviour of Glutamine Peptides

Baskar¹,

Shafique²,

Nandel³

2014

JBPC

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Trinucleotide repeat expansions (CAG) lead to increase in glutamine residues and hence increase in glutamine stretch. This leads to number of neurodegenerative diseases. Therefore, the conformation of poly Q of varying chain lengths has been investigated by quantum mechanical and molecular dynamics approaches. Glutamine contains amide linkage in the side chain. It is the interaction between side chain amide linkage and the peptide bond of the backbone which dictates the conformational behaviour. Some of the glutamine residues adopt phi psi values corresponding to poly-L-proline type II structure. Not more than three glutamine residues are found to have the same set of ϕ, ѱ values and hence polyglutamine is adopting random coil structure. Carbonyl-carbonyl, CH-O interactions and hydrogen bond formation involving backbone and side chain amide chain linkages are found to contribute to the stability of the adopted structure. In simulation studies due to interaction of water molecules with the amide linkages the ϕ, ѱ values undergo change and this leads to weakening of carbonyl-carbonyl interactions and hydrogen bonds. The conformational behaviour of polyglutamine peptides is shown to be chain length dependent and this may provide some insight regarding the aggregation behaviour of proteins containing poly Q stretch. Possibly this is the first systematic study of the conformational behaviour of polyglutamine peptides.

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Molecular dynamics simulation of the transmembrane subunit of BtuCD in the lipid bilayer

Cited by 10 publications

References 46 publications

Insights on P-Glycoprotein’s Efflux Mechanism Obtained by Molecular Dynamics Simulations

Insights on P-Glycoprotein’s Efflux Mechanism Obtained by Molecular Dynamics Simulations

Molecular-Dynamics Simulations of the ATP/apo State of a Multidrug ATP-Binding Cassette Transporter Provide a Structural and Mechanistic Basis for the Asymmetric Occluded State

A Unique Conformational Behaviour of Glutamine Peptides

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