246
M. Melicherčík et al.
in liquid crystalline state were performed by Esteban-Martнn and Salgado [48].
They studied WLP 23 (acetyl-G-W 2 -L 17 -W 2 -A-ethanolamine) and KLP 23 in DMPC
bilayers and observed faster relaxation of Lys-flanked peptides (~10 ns) but lower
tilt angle (~20°), while Trp-flanked ones relaxed during 50 ns (in some simulations
even till 150 ns), but the final tilt was ~31°. Based on experimental data [49, 50]
they stated the hypothesis that the 200 ns simulation is not enough to fully relax the
system. Certainly, the measured tilt by
2
H-NMR quadrupole splittings is lower than
in simulated systems.
Davies et al. studied phase transitions with
2
H-NMR quadruple splittings spectra.
The longer peptides L 24 in DPPC membrane in peptide to lipid molar ratio of 100:1
caused 30 % increase of order in lipids acyl chains, while in molar ratio of 43:1 there
was only 5 % order increase [11]. In Pan et al. X-ray experiments and MD simulations [51] of alamecithin it has been shown that this peptide decreases thickness of
diC22:1-PC membrane and increases its own length in a peptide to lipid molar ratio
of 1:10. However, in a DOPC membrane this peptide tilts in approx. ~15°. In both
cases the peptide decreased of membrane fluctuations (bending modulus K c ), but
the diC22:1-PC is more stabilized (factor ~10) than DOPC (only ~2).
Other peptide, the maculatin 1.1, remains in helical conformation in bilayers of
wide range of lipid composition (DHPC to DPPC, POPC, DOPC, DMPA, DMPS,
DPPS and DMPG). Only exceptions were the DHPC/LQ and DPPC in liquid crystalline and gel phases, respectively, where there is the too large difference between
hydrophobic lengths of membrane and peptide [52].
Hoernke et al. [53] used modified Lys-flanked peptides and those in which Lys
has been replaced by ornithine, α,γ-diaminobutyric acid, α,β-diaminopropionic acid
in negatively charged phosphatidyl glycerol (PG) membrane. These smaller sidechains caused higher increase of phase transitions temperature and decrease of surface pressure. The long polylysines (more Lys residues at the ends) increase phase
transitions temperature, but short ones lower it.
8.1.2 Mutation Studies
Johannson and Lindhal [54] tested systematic mutations of acetyl-G 2 PG-A 19 -GPG 2 -
amid peptide in DMPC membrane. Some amino acids did dissolve completely in
hydrophobic part of the membrane, but caused surface defects and water snorkeling
into membrane. This suggests that even for polar/charged residues a large part of
solvation cost is due to entropy, not enthalpy losses. Basic side chains cause much
less membrane distortion than acidic, since they are able to form hydrogen bonds
with carbonyl groups instead of water or other lipid headgroups. This preference
is supported by sequence statistics, where basic residues have increased relative
occurrence at carbonyl z-coordinates. Snorkeling effects and N-/C-terminal orientation bias are directly observed, which significantly reduces the effective thickness of the hydrophobic core. Aromatic side chains intercalate efficiently with lipid
chains (improving Trp/Tyr anchoring to the interface) and Ser/Thr residues are stabilized by hydroxyl groups sharing hydrogen bonds to backbone oxygens.
M. Melicherčík et al.
in liquid crystalline state were performed by Esteban-Martнn and Salgado [48].
They studied WLP 23 (acetyl-G-W 2 -L 17 -W 2 -A-ethanolamine) and KLP 23 in DMPC
bilayers and observed faster relaxation of Lys-flanked peptides (~10 ns) but lower
tilt angle (~20°), while Trp-flanked ones relaxed during 50 ns (in some simulations
even till 150 ns), but the final tilt was ~31°. Based on experimental data [49, 50]
they stated the hypothesis that the 200 ns simulation is not enough to fully relax the
system. Certainly, the measured tilt by
2
H-NMR quadrupole splittings is lower than
in simulated systems.
Davies et al. studied phase transitions with
2
H-NMR quadruple splittings spectra.
The longer peptides L 24 in DPPC membrane in peptide to lipid molar ratio of 100:1
caused 30 % increase of order in lipids acyl chains, while in molar ratio of 43:1 there
was only 5 % order increase [11]. In Pan et al. X-ray experiments and MD simulations [51] of alamecithin it has been shown that this peptide decreases thickness of
diC22:1-PC membrane and increases its own length in a peptide to lipid molar ratio
of 1:10. However, in a DOPC membrane this peptide tilts in approx. ~15°. In both
cases the peptide decreased of membrane fluctuations (bending modulus K c ), but
the diC22:1-PC is more stabilized (factor ~10) than DOPC (only ~2).
Other peptide, the maculatin 1.1, remains in helical conformation in bilayers of
wide range of lipid composition (DHPC to DPPC, POPC, DOPC, DMPA, DMPS,
DPPS and DMPG). Only exceptions were the DHPC/LQ and DPPC in liquid crystalline and gel phases, respectively, where there is the too large difference between
hydrophobic lengths of membrane and peptide [52].
Hoernke et al. [53] used modified Lys-flanked peptides and those in which Lys
has been replaced by ornithine, α,γ-diaminobutyric acid, α,β-diaminopropionic acid
in negatively charged phosphatidyl glycerol (PG) membrane. These smaller sidechains caused higher increase of phase transitions temperature and decrease of surface pressure. The long polylysines (more Lys residues at the ends) increase phase
transitions temperature, but short ones lower it.
8.1.2 Mutation Studies
Johannson and Lindhal [54] tested systematic mutations of acetyl-G 2 PG-A 19 -GPG 2 -
amid peptide in DMPC membrane. Some amino acids did dissolve completely in
hydrophobic part of the membrane, but caused surface defects and water snorkeling
into membrane. This suggests that even for polar/charged residues a large part of
solvation cost is due to entropy, not enthalpy losses. Basic side chains cause much
less membrane distortion than acidic, since they are able to form hydrogen bonds
with carbonyl groups instead of water or other lipid headgroups. This preference
is supported by sequence statistics, where basic residues have increased relative
occurrence at carbonyl z-coordinates. Snorkeling effects and N-/C-terminal orientation bias are directly observed, which significantly reduces the effective thickness of the hydrophobic core. Aromatic side chains intercalate efficiently with lipid
chains (improving Trp/Tyr anchoring to the interface) and Ser/Thr residues are stabilized by hydroxyl groups sharing hydrogen bonds to backbone oxygens.