Table 1.
Summary of molecular dynamics simulation systems.
Fig 1.
Conformational analysis of BMAP27 in aqueous and model lipid-bilayer environments.
BMAP27 folding studied in (A) AMBER99SB-ILDN, and (B) CHARMM36 force field on a 0.5 μs time scale. The peptide and solvent molecules are represented as schematic and lines in Discovery studio visualizer 3.5, respectively. The peptide is colored by its hydrophobicity where hydrophobic and hydrophilic residues are shown as brown and blue, respectively. The partial density changes across the corresponding simulation boxes are shown in the central column. The z-coordinate represents the peptide position inside the simulation box. BMAP27 interaction with (C) zwitterionic (POPC), and (D) anionic (DOPG) membrane model systems. The peptide conformation is shown as a cartoon, lipid in blue line and water as red lines in VMD program. The relative BMAP27 membrane penetration is calculated by plotting the center of mass of peptide and lipid head phosphates present in the outer leaflets.
Fig 2.
Partial density analysis of peptide, lipid, water and ions in different lipid-bilayer systems.
(A) POPC, (B) DOPG membrane system. The outer and inner leaflets of the bilayer membrane are denoted as OL and IL, respectively. The contribution of various types of atoms are shown in the graph in different colors during the 0.5 μs MD simulation. (C) Potential of mean force acting on the BMAP27 to penetrate the lipid bilayer membrane. The horizontal axis shows the distance between the peptide and lipid bilayer membrane with the bilayer core situated at z = 0. The peptide molecule insertion path is perpendicular to the bilayer surface. The PMF calculation in BMAP27mut system is carried out only for the anionic systems and are compared with the PMF values of wild type BMAP27.
Table 2.
Average number of hydrogen bonds between membrane lipids and BMAP27 residues.
Fig 3.
Interaction of BMAP27 with TLM and LLM systems in all-atom MD simulation.
(A) The graph illustrates the center of mass of BMAP27 (full-length), helix (3–16), C-terminal residues (17–26) and lipid phosphate atoms. (B) Illustration of interaction of BMAP27 with the LLM. The peptide and lipids are shown as a cartoon and line in PyMOL. The hydrogen bonds between BMAP27 and lipid molecules are shown in black dotted lines. The hydrophobic residues and their solvent exposed side chains are shown in blue. The crucial kink position at F10 is shown as bold and red. (C) Center of mass analysis of BMAP27 in the TLM system. (D) Conformational alternation of BMAP27 and its interaction with the TLM model.
Fig 4.
Coarse-grained MD models illustrating interaction between BMAP27 and lipid-bilayers.
Snapshots of BMAP27 interacting with (A) DPPC model membrane during 10 μs time period, (B) DOPG model membrane during 10 μs time period, (C) TLM model membrane during 20 μs time period, and (D) LLM model membrane during 20 μs time period. The graphics are generated using VMD program. The α-helices of four different BMAP27 molecules are shown as blue, black, red and green in VDW format and their C-terminal hydrophobic residues as yellow. The lipid molecule types are represented in CPK format.
Fig 5.
Representation of end-to-end and micelle-like BMAP27 oligomer interaction.
(A) End-to-end arrangement, and (B) micelle-like arrangement. The all-atom and coarse-grained models of peptide oligomers are shown as a cartoon and spheres, respectively, and are colored by chains. The relative peptide penetration is calculated from its center of mass to the outer leaflet lipid phosphate atoms as a function of time. The peptide and lipid phosphate atoms are shown in red and blue VDW formats, respectively, in VMD program. Vertical dotted lines divide both leaflets symmetrically and the black arrows indicate the membrane groove formation upon peptide binding. The abbreviations OL and IL denote outer-leaflet and inner-leaflets, respectively. The cyan arrows indicate monomer formation in the end-to-end model system.
Fig 6.
Illustration of BMAP27 interaction and penetration during the multi-μs coarse-grained MD simulation.
BMAP27 interaction in (A) DPPC, (B) DOPS, (C) TLM, and (D) LLM model systems. The peptide monomers are colored by chain and shown as tan, black, red and green, and the C-terminal residues as yellow in VDW format in VMD program. The outer and inner leaflets of each bilayer system are denoted as OL and IL, respectively. The vertical dotted line drawn indicates the symmetric division of the total distance between the OL and IL. The center of mass graphs representing the peptide penetration is shown with respect to the lipid head atoms for individual systems and are presented below their corresponding molecular structures.
Fig 7.
Measurement of bilayer thickness in coarse-grained systems using GridMAT-MD program.
The graphics were generated by gnuplot 4.6 using a 20 x 20 matrix distribution. The thickness change monitored through the different colors in the graph are correlated with the distance scale (nanometer) given on the right-hand side of the individual systems. For each system two graphs are shown representing the bilayer thickness before MD (in absence of peptide) and after MD (with peptide) simulation.