Research article

Simulation of lipid-protein interactions with the CgProt force field

  • Received: 13 July 2017 Accepted: 17 September 2017 Published: 22 September 2017
  • The effect of lipid-protein interactions on membrane proteins and their function is emerging as an important area in biophysics. The recently developed CgProt force field is used to explore molecular level interactions in peptides and proteins through coarse-grained molecular dynamics simulations in the presence of the lipid bilayer environment. The mechanism of membrane insertion was examined for designed helical peptides WALP27: GWW(LA)10LWWA and LS3: (LSSLLSL)3. WALP27 adopts a transmembrane conformation while LS3 adopts interfacial and transmembrane orientations in independent simulations from different starting conditions. A total of 13 peptide insertion events were observed in unbiased molecular dynamics simulations of LS3 and WALP. Each case proceeded via the charged N-terminus crossing the bilayer. In the equilibrated conformations, the C-terminus resides in the head group region of the DOPC bilayer, while the N-terminus submerges deep into the carbonyl region. These findings are consistent with recent evidence of the attractive nature of positive charges for the membrane interface. The role of lipid interactions in the native environment of a membrane protein was explored by simulation of a 12-transmembrane helix multidrug transporter, P-glycoprotein. Analysis of the lipid density in a POPC: POPE bilayer containing 20% cholesterol revealed an annular solvation shell of phosphatidyl choline and cholesterol that diffuses with the protein in the membrane. The inward-facing state of P-glycoprotein undergoes a conformational transition to the closed state, corroborating a structural model for the ATP-bound state recently generated by homology modeling and molecular dynamics simulation.

    Citation: Jacob Fosso-Tande, Cody Black, Stephen G. Aller, Lanyuan Lu, Ronald D. Hills Jr. Simulation of lipid-protein interactions with the CgProt force field[J]. AIMS Molecular Science, 2017, 4(3): 352-369. doi: 10.3934/molsci.2017.3.352

    Related Papers:

  • The effect of lipid-protein interactions on membrane proteins and their function is emerging as an important area in biophysics. The recently developed CgProt force field is used to explore molecular level interactions in peptides and proteins through coarse-grained molecular dynamics simulations in the presence of the lipid bilayer environment. The mechanism of membrane insertion was examined for designed helical peptides WALP27: GWW(LA)10LWWA and LS3: (LSSLLSL)3. WALP27 adopts a transmembrane conformation while LS3 adopts interfacial and transmembrane orientations in independent simulations from different starting conditions. A total of 13 peptide insertion events were observed in unbiased molecular dynamics simulations of LS3 and WALP. Each case proceeded via the charged N-terminus crossing the bilayer. In the equilibrated conformations, the C-terminus resides in the head group region of the DOPC bilayer, while the N-terminus submerges deep into the carbonyl region. These findings are consistent with recent evidence of the attractive nature of positive charges for the membrane interface. The role of lipid interactions in the native environment of a membrane protein was explored by simulation of a 12-transmembrane helix multidrug transporter, P-glycoprotein. Analysis of the lipid density in a POPC: POPE bilayer containing 20% cholesterol revealed an annular solvation shell of phosphatidyl choline and cholesterol that diffuses with the protein in the membrane. The inward-facing state of P-glycoprotein undergoes a conformational transition to the closed state, corroborating a structural model for the ATP-bound state recently generated by homology modeling and molecular dynamics simulation.


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