248
M. Melicherčík et al.
mismatch; (4) the minimum-PMF tilt angle is generally located where there is the
hydrophobic match and little lipid perturbation; (5) TM helix rotation is dependent
on the specific helix-lipid interactions; (6) anchoring residues at the hydrophilic/
hydrophobic interface can be an important determinant of TM helix orientation.
Also at large peptide tilt angles the surrounding membrane is even thinner than
pure membrane. The tilt angles of different flanking residues depend on its hydrophobicity—lowest tilt angle has RALP peptide in comparison with other peptides:
RALP < KALP < WALP < AALP. The authors also compared MD results with previous published experimental data for similar peptides obtained by
2
H-NMR splitting
measurements (for example the tilt angles have been 4.4° for KALP 23 and 5.2°
for WALP 23 ) [61, 62]. They concluded that for correct determination of tilt angles
from splittings data, the proper averages of rotation angles is necessary, as it has
been done in Ref. [63–65]. For example the florescence spectroscopy determined
WALP 23 /DOPC tilt angle 24° ± 5° [65].
Monticelli et al. [66] published another comparison of
2
H-NMR quadrupole
splittings and MD simulations. They used WALP 23 in DMPC and stated that the
underestimation of peptide movements can affect the measured tilt angle. This has
been also concluded in [63, 64], where authors recognized the problem in GALA
method (geometric analysis of labeled alanines) with position averaging. They used
nonlinear averaging of goniometric functions and showed that the peptide in membrane tilted by 30° can have the same quadrupolar samplings as motionless peptide
with 5° tilt.
In this chapter we show usefulness of the molecular dynamics simulations on the
study of model helical peptides composed of acetyl-K 2 -A 24 -K 2 -amide (A 24 ), acetyl-K 2 -L 24 -K 2 -amide (L 24 ), acetyl-K 2 -(LA) 12 -K 2 -amide ((LA) 12 ), acetyl-K 2 -I 24 -K 2 -
amide (I 24 ), acetyl-K 2 -G-L 24 -K 2 -A-amide (P 24 ) and acetyl-K 2 -V 24 -K 2 -amide (V 24 )
incorporated into the phospholipid bilayers (DMPC, DPPC). The behavior of some
of these and other peptides in membranes of various lipid compositions has been
analyzed by Host and Killian [67]. We have shown that the effect of peptides on the
lipid bilayer strongly depends on membrane physical state—gel or liquid crystalline.
8.2 Methods
MD has been applied for the determination of changes of physical properties of
lipid bilayers caused by the incorporated peptide as well as for the determination of possible peptide structural alterations. MD were performed under periodic
boundary conditions using the GROMACS software [68] and the GROMOS87 [69]
forcefield with corrections for lipids [70, 71]. The initial models of transmembrane
α-helix peptides have been generated by means of HyperChem [72]. Preequilibrated
DMPC and DPPC bilayers with 128 lipid molecules and 3655 molecules of water
in L α liquid-crystalline state published by Tieleman et al. [73] have been used in
bilayer modeling. For the simulations with membrane in L β ’ gel state, we created
M. Melicherčík et al.
mismatch; (4) the minimum-PMF tilt angle is generally located where there is the
hydrophobic match and little lipid perturbation; (5) TM helix rotation is dependent
on the specific helix-lipid interactions; (6) anchoring residues at the hydrophilic/
hydrophobic interface can be an important determinant of TM helix orientation.
Also at large peptide tilt angles the surrounding membrane is even thinner than
pure membrane. The tilt angles of different flanking residues depend on its hydrophobicity—lowest tilt angle has RALP peptide in comparison with other peptides:
RALP < KALP < WALP < AALP. The authors also compared MD results with previous published experimental data for similar peptides obtained by
2
H-NMR splitting
measurements (for example the tilt angles have been 4.4° for KALP 23 and 5.2°
for WALP 23 ) [61, 62]. They concluded that for correct determination of tilt angles
from splittings data, the proper averages of rotation angles is necessary, as it has
been done in Ref. [63–65]. For example the florescence spectroscopy determined
WALP 23 /DOPC tilt angle 24° ± 5° [65].
Monticelli et al. [66] published another comparison of
2
H-NMR quadrupole
splittings and MD simulations. They used WALP 23 in DMPC and stated that the
underestimation of peptide movements can affect the measured tilt angle. This has
been also concluded in [63, 64], where authors recognized the problem in GALA
method (geometric analysis of labeled alanines) with position averaging. They used
nonlinear averaging of goniometric functions and showed that the peptide in membrane tilted by 30° can have the same quadrupolar samplings as motionless peptide
with 5° tilt.
In this chapter we show usefulness of the molecular dynamics simulations on the
study of model helical peptides composed of acetyl-K 2 -A 24 -K 2 -amide (A 24 ), acetyl-K 2 -L 24 -K 2 -amide (L 24 ), acetyl-K 2 -(LA) 12 -K 2 -amide ((LA) 12 ), acetyl-K 2 -I 24 -K 2 -
amide (I 24 ), acetyl-K 2 -G-L 24 -K 2 -A-amide (P 24 ) and acetyl-K 2 -V 24 -K 2 -amide (V 24 )
incorporated into the phospholipid bilayers (DMPC, DPPC). The behavior of some
of these and other peptides in membranes of various lipid compositions has been
analyzed by Host and Killian [67]. We have shown that the effect of peptides on the
lipid bilayer strongly depends on membrane physical state—gel or liquid crystalline.
8.2 Methods
MD has been applied for the determination of changes of physical properties of
lipid bilayers caused by the incorporated peptide as well as for the determination of possible peptide structural alterations. MD were performed under periodic
boundary conditions using the GROMACS software [68] and the GROMOS87 [69]
forcefield with corrections for lipids [70, 71]. The initial models of transmembrane
α-helix peptides have been generated by means of HyperChem [72]. Preequilibrated
DMPC and DPPC bilayers with 128 lipid molecules and 3655 molecules of water
in L α liquid-crystalline state published by Tieleman et al. [73] have been used in
bilayer modeling. For the simulations with membrane in L β ’ gel state, we created