This thesis describes the combination of experimental (neutron diffraction) and
computational techniques (molecular dynamics simulations) to investigate membrane
peptide interactions.The first part deals with a comparison of human and rat form of the amyloid inducing
peptide islet amyloid polypeptide (IAPP). Lamellar neutron diffraction was performed
and a structural comparison on the differing modes of actions of the rat and human
forms of IAPP are reported.A computational model for a di-oleoyl phosphatidylcholine (DOPC) bilayer was then
constructed. Once this bilayer had been verified with experimental data (namely area per
headgroup, volume per lipid, order parameter of the oleoyl chains and electron density
profile) a mixed bilayer of DOPC and di-oleoyl phopshatidylglycerol (DOPG) was then
constructed. The mixed bilayer was verified in the same mannerA peptide (adenosine diphosphate ribosylation factor-1 (pARF-1)) was then inserted
into the pre-equilibrated mixed bilayer. The orientation of this peptide with respect to
the membrane was based on previous neutron diffraction studies, carried out by other
group members. Four possible orientations had resulted from analysis of the neutron
data. The four orientations of pARF-1 were then subjected to molecular dynamics
simulations. The time course of these simulations was 4 ns. The simulation's
trajectories were analysed for each of the four models. Particular emphasis was placed
upon the positional changes of the phenylalanine label positions that were derived from
the neutron data. It was concluded that model A was the most likely orientation of
pARF-1 in relation to the bilayer.Having established the technique, and confirmed that the most likely orientation of the
peptide was what was originally proposed, another peptide, the fusion peptide of simian
immunodeficiency virus (SIV) was placed into a previously equilibrated DOPC bilayer.
In this case, only the proposed orientation of the SIV fusion peptide in relation to the
bilayer was studied utilizing molecular dynamics simulations. The results are
interpreted in relation to the actions of SIV fusion peptide upon the membrane, with
particular emphasis on the disruption of oleoyl chain order parameters and secondary
structure of the membrane bound fusion peptide
