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

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.

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• Anharmonic and Quantum Fluctuations in Molecular Crystals: A First-Principles Study of the Stability of Paracetamol
• Inverse Temperature Dependence of Nuclear Quantum Effects in DNA Base Pairs
• Decisive role of nuclear quantum effects on surface mediated water dissociation at finite temperature
• Quantum dynamics using path integral coarse-graining
• Phase behaviour of the quantum Lennard-Jones solid