Stability of Complex Biomolecular Structures: van der Waals, Hydrogen Bond Cooperativity, and Nuclear Quantum Effects

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.