title: Bindings of hMRP1 transmembrane peptides with dodecylphosphocholine and dodecyl-β-d-maltoside micelles: a molecular dynamics simulation study.
abstract: In this paper, we describe molecular dynamics simulation results of the interactions between four peptides (mTM10, mTM16, TM17 and KTM17) with micelles of dodecylphosphocholine (DPC) and dodecyl-β-d-maltoside (DDM). These peptides represent three transmembrane fragments (TM10, 16 and 17) from the MSD1 and MSD2 membrane-spanning domains of an ABC membrane protein (hMRP1), which play roles in the protein functions. The peptide-micelle complex structures, including the tryptophan accessibility and dynamics were compared to circular dichroism and fluorescence studies obtained in water, trifluoroethanol and with micelles. Our work provides additional results not directly accessible by experiments that give further support to the fact that these peptides adopt an interfacial conformation within the micelles. We also show that the peptides are more buried in DDM than in DPC, and consequently, that they have a larger surface exposure to water in DPC than in DDM. As noted previously by simulations and experiments we have also observed formation of cation-π bonds between the phosphocholine DPC headgroup and Trp peptide residue. Concerning the peptide secondary structures (SS), we find that in TFE their initial helical conformations are maintained during the simulation, whereas in water their initial SS are lost after few nanoseconds of simulation. An intermediate situation is observed with micelles, where the peptides remain partially folded and more structured in DDM than in DPC. Finally, our results show no sign of β-strand structure formation as invoked by far-UV CD experiments even when three identical peptides are simulated either in water or with micelles.
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, DSV/iBiTEC-S/SB2SM/LBMS & CNRS UMR 8221, Saclay, France. Electronic address: stephane.abel@cea.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Abel
authors.forename: Anaïs
authors.initials: A
authors.lastname: Lorieau
authors.forename: Béatrice
authors.initials: B
authors.lastname: de Foresta
authors.forename: François-Yves
authors.initials: FY
authors.lastname: Dupradeau
authors.forename: Massimo
authors.initials: M
authors.lastname: Marchi
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005960:Glucosides / Q000737:chemistry*; D006801:Humans; D008823:Micelles; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D005960:Glucosides; D008823:Micelles; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010455:Peptides; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; C040358:dodecyl maltoside; C421109:multidrug resistance-associated protein 1
keywords: Dodecyl-β-d-maltoside micelle; Dodecylphosphocholine; Molecular dynamics; Peptide–micelle interaction; Transmembrane peptide fragment; hMRP1 (ABCC1)