The Structure of Intrinsically Disordered Peptides Implicated in Amyloid Diseases: Insights from Fully Atomistic Simulations - Computational Modeling of Biological Systems - page 222

Fig. 4 Schematic representation of a possible oligomerization mechanism, adapted from [ 65 ].
Among two interconverting structural families of human IAPP, “-hairpins are proposed to self-
assemble into early ordered human IAPP oligomers by side-to-side association. The (?) symbol
notes that we have no data pro or con the occurrence of this mechanism and we hence include it
for completeness

5 Conclusions

Fully atomic simulations, coupled with enhanced sampling techniques, are emerg-
ing as powerful tools for the study of intrinsically disordered peptides. While most
experimental techniques only provide ensemble averaged information, simulations
are capable of providing detailed atomistic information about the structures popu-
lated by these peptides. A highlight of the simulations described in the preceding
paragraph is the identification of “-rich conformers, coexisting with non-“-rich
structures that may play a role in initiating aggregation. With ever increasing
computational power and sophisticated sampling schemes, simulations are now
poised to move beyond the investigation of aggregating IDP peptides in a bulk-
like environment to the study of the interaction of these peptides with membranes
[ 74 - 80 ]. A long-term goal of these simulations is to prove detailed structural
information that can guide the rational design of drugs as therapeutics for amyloid
diseases.