Nanosolvation-induced
stabilization of a protonated
peptide dimer isolated
in the gas phase
The structure and functionality of bio-
molecules, as well as their susceptibility
to external factors (such as ionizing
radiation), are intrinsically linked with
their aqueous environment. The structure-
function paradigm postulates that proteins
are required to adopt a specific folding
to be biologically active. Weak molecular
interactions have been proposed to have
a major role in protein folding and in the
formation of macromolecular complexes.
In particular, the solvent has a key role
in self-assembling processes. The recent
measurements performed at DESIRS
beamline, combined with theoretical study
on protonated leucine–enkephalin peptide
dimer ion, have shown that nanosolvation
of a fragile biomolecular complex by only
a few water molecules appears to have
a dramatic impact on its stability.
The need to gain a deeper understanding
of the effect of water solvation on the
protein structure has led to an intensive
investigation of gradual solvation of
biomolecules – the limit of the so called
microsolvation (or nanosolvation), referring
to only a small and well-defined number
of attached water molecules, has been
conceived. However, the experimental
investigation of nanosolvated species
under well-defined conditions is
challenging. We report a comparative
experimental and theoretical study on
the bare protonated leucine–encephalin
(Leu-Enk) peptide dimer ion and on the
same system hydrated with three water
molecules, showing already a clear
nanosolvation effect. The Leu-Enk dimer
is used here as a model system for
peptide–peptide interactions, which
is pertinent not only for non-covalent
complex formation but also for the
acquisition of secondary and ternary
structures of proteins.
By using a recently developed
experimental setup [1], in which an ion
trap mass spectrometer equipped with
electrospray sources is coupled to the
DESIRS VUV beamline, it has been possible
to isolate in the gas either the bare
or the hydrated precursor, and to measure
the photon-induced fragmentation
intensity at different photon energies
(figure
➊
). The results showed a drastic
suppression of both the hydrated precursor
dissociation into monomers (figure
➋
-
top) and the peptide backbone cleavage,
thus clearly demonstrating a significant
stabilization of the system due to the
addition of only a few water molecules.
Furthermore, the solvation-induced
stability was substantiated by detecting
the doubly charged ion produced upon
photoionization of the hydrated protonated
species, which can be preserved in the
gas phase, thus also allowing a precise
determination of the ionization threshold
(figure
➋
- bottom). The apparent
increased stability toward VUV irradiation
of the hydrated complex with respect
to the bare species is striking and
questions the energy dissipation process,
since the nanosolvation produces
a frustrated dissociation in the dimer
even for irradiation at energies below
the ionization threshold.
Theoretical study, employing molecular
dynamics and density functional theory
(DFT) calculations, of the structure
of the nanosolvated peptide dimer is
consistent with the experimental findings.
The calculations show that hydration
with only 3 water molecules does not
affect significantly the 3D structure of
the dimer (figure
➌
), but rather stabilizes
it by about 1.5 eV. Actually, the dimer is
formed via non-covalent bonds (H-bonds)
both in the bare and the solvated case.
However, the binding is strongly enhanced
upon nanosolvation, due to the flexibility
of H
2
O to adjust its bridging position
and orientation with respect to the other
molecules, thus increasing the effective
number of hydrogen bonds.
The present results are important to
consider when stability of protein non-
covalent complexes and protein structure
is assessed for isolated non-hydrated
ions, by mass spectrometry for example.
Moreover, the phenomenological shielding
effect of microsolvation observed here is
of interest in the field of radiation damage
and could help in the future to have
a better understanding of these processes
at the molecular level.
ATOMIC AND MOLECULAR PHYSICS, DILUTE MATTER, UNIVERSE SCIENCE
86
SOLEIL
HIGHLIGHTS
2013
