  Biomolecules are complex systems stabilized by a delicate balance of weak
interactions, making it important to assess all energetic contributions in an
accurate manner. However, it is a priori unclear which contributions make more
of an impact. Here, we examine stacked polyglutamine (polyQ) strands, a peptide
repeat often found in amyloid aggregates. We investigate the role of hydrogen
bond (HB) cooperativity, van der Waals (vdW) dispersion interactions, and
quantum contributions to free energies, including anharmonicities through
density functional theory and ab initio path integral simulations. Of these
various factors, we find that the largest impact on structural stabilization
comes from vdW interactions. HB cooperativity is the second largest
contribution as the size of the stacked chain grows. Competing nuclear quantum
effects make the net quantum contribution small but very sensitive to
anharmonicities, vdW, and the number of HBs. Our results suggest that a
reliable treatment of these systems can only be attained by considering all of
these components.
