Intermolecular structure and dynamics of aqueous N-methylacetamide
Date
2007Author
Allison, Susan
Metadata
Abstract
The twin questions of how and why protein molecules fold into the specific topologies
which enable them to fulfill their biological function have been the subject of continuous
scientific investigation since the early twentieth century. Interactions between biological
macromolecules and water are obviously crucial to both folding and function but
attempts to gain understanding are impeded by the size and complexity of these
systems. A useful approach is to consider much simpler model systems which
capture some essential element of real biological systems but are experimentally and
theoretically tractable.
N-methylacetamide (NMA) is a minimal model of the peptide linkage which forms the
backbone of protein molecules. Its behaviour in aqueous solution therefore captures the
important competition between peptide - peptide and peptide - water hydrogen bonds
which arises in protein hydration. In this thesis aqueous NMA solutions are studied
across the full concentration range using classical molecular dynamics simulation. This
gives access to the complete spectrum of behaviour between the two important limiting
cases of dilute NMA in water and, conversely, dilute water in NMA.
Water is now known to be an active player in biological interactions and the simple
system studied here displays significant disruption of the structure and dynamics of
pure water with the addition of only a small proportion of peptide groups. At dilute
NMA concentrations water molecules continue to form system-size hydrogen bonded
networks. Water molecules appear to optimise their local tetrahedral order by forming
hydrogen bonds with a combination of NMA and water neighbours, rather than solely
with members of their own species.
NMA molecules hydrogen bond through the amide and carbonyl groups to form linear
and branched chains in both the pure liquid and in the aqueous solutions. In the NMA rich
region water molecules preferentially donate both hydrogens to chain-end or midchain
carbonyl oxygens, forming bridges between NMA chains which resemble buried
water configurations found in protein cavities. These bridge structures are thought to
contribute to the observed slowing of the system dynamics at these concentrations.
The investigation of dynamics by classical simulation is complemented by a quasielastic
neutron scattering study of NMA in its liquid and aqueous phases.