title: Stability of Complex Biomolecular Structures: van der 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.
authors.affiliation: Physical and Theoretical Chemistry Lab, University of Oxford , South Parks Road, OX1 3QZ Oxford, United Kingdom.|St. Edmund Hall , Queen's Lane, OX1 4AR Oxford, United Kingdom.
authors.forename: Mariana
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Thomas Young Centre, London Centre for Nanotechnology, and Department of Chemistry, University College London , 17-19 Gordon Street, WC1H 0AH London, United Kingdom.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Thomas Young Centre, London Centre for Nanotechnology, and Department of Chemistry, University College London , 17-19 Gordon Street, WC1H 0AH London, United Kingdom.
authors.forename: Angelos
authors.initials: A
authors.lastname: Michaelides
mesh_terms: D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011789:Quantum Theory
chemical_list: D010455:Peptides; C097188:polyglutamine
keywords: amyloid; cooperativity; electronic structure; polyglutamine; van der Waals