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

TL;DR

This study investigates the energetic contributions stabilizing biomolecular structures, emphasizing van der Waals interactions, hydrogen bond cooperativity, and nuclear quantum effects, highlighting the importance of comprehensive modeling for accurate understanding.

Contribution

It provides a detailed analysis of the relative impacts of vdW, HB cooperativity, and quantum effects on biomolecular stability using advanced computational methods.

Findings

vdW interactions have the largest impact on stabilization

HB cooperativity increases with chain length

Quantum effects are small but highly sensitive to other factors

Abstract

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.