  As the beneficial effects of curcumin have often been reported to be limited
to its small concentrations, we have undertaken a study to find the aggregation
properties of curcumin in water by varying the number of monomers. Our
molecular dynamics simulation results show that the equilibrated structure is
always an aggregated state with remarkable structural rearrangements as we vary
the number of curcumin monomers from 4 to 16 monomers. We find that curcumin
monomers form clusters in a very definite pattern where they tend to aggregate
both in parallel and anti-parallel orientation of the phenyl rings, often seen
in the formation of beta-sheet in proteins. A considerable enhancement in the
population of parallel alignments is observed with increasing the system size
from 12 to 16 curcumin monomers. Due to the prevalence of such parallel
alignment for large system size, a more closely packed cluster is formed with
maximum number of hydrophobic contacts. We also follow the pathway of cluster
growth, in particular the transition from the initial segregated to the final
aggregated state. We find the existence of a metastable structural intermediate
involving a number of intermediate-sized clusters dispersed in the solution.
The course of aggregation bears similarity to nucleation and growth in highly
metastable state. The final aggregated form remains stable with total exclusion
of water from its sequestered hydrophobic core. We also investigate water
structure near the cluster surface along with their orientation. We find that
water molecules form a distorted tetrahedral geometry in the 1st solvation
layer of the cluster, interacting strongly with hydrophilic groups at the
surface of curcumin. The dynamics of such quasi-bound water molecules near the
surface of curcumin cluster is considerably slower than the bulk signifying a
restricted motion as often found in protein hydration layer.
