Adsorption Mechanism and Collapse Propensities of the Full-Length, Monomeric Aβ1-42 on the Surface of a Single-Walled Carbon Nanotube: A Molecular Dynamics Simulation Study

Abstract

Though nanomaterials such as carbon nanotubes have gained recent attention in biology and medicine, there are few studies at the single-molecule level that explore their interactions with disease-causing proteins. Using atomistic molecular-dynamics simulations, we have investigated the interactions of the monomeric Aβ(1-42) peptide with a single-walled carbon nanotube of small diameter. Starting with peptide-nanotube complexes that delineate the interactions of different segments of the peptide, we find rapid convergence in the peptide's adsorption behavior on the nanotube surface, manifested in its arrested movement, the convergence of peptide-nanotube contact areas and approach distances, and in increased peptide wrapping around the nanotube. In systems where the N-terminal domain is initially distal from nanotube, the adsorption phenomena are initiated by interactions arising from the central hydrophobic core, and precipitated by those arising from the N-terminal residues. Our simulations and free energy calculations together demonstrate that the presence of the nanotube increases the energetic favorability of the open state. We note that the observation of peptide localization could be leveraged for site-specific drug delivery, while the decreased propensity of collapse appears promising for altering kinetics of the peptide's self-assembly.

Enhanced Sampling in Molecular Dynamics Using Metadynamics, Replica-Exchange, and Temperature-Acceleration

“…(1) Peptide backbone angle sampling [36,37]; (2) Nucleoside [38], protein [39] and fullerene [40,41] insertion into a lipid bilayer; (3) Interactions of small molecules with polymers in water [42,43]; (4) Molecule/ion transport through protein complexes [44][45][46][47] and DNA superstructures [48]; (5) Calculation of octanol-water partition coefficients [49,50]; (6) Large-scale protein conformational changes [51]; (7) Protein-nanotube [52] and nanotube-nanotube [53] association.…”

Computational Approaches to Understanding the Biological Behaviour of Intrinsically Disordered Proteins

“…Protein surface interactions have been capturing increasing attention owing to their ubiquitous occurrence in biological processes and a wide range of applications in bioengineering and nanotechnology 30,[103][104][105] . Understanding protein-surface interactions is key to the development of new strategies in the field of nanomedicine, biomaterial sciences and nanobiotechnology.…”

“…Understanding protein-surface interactions is key to the development of new strategies in the field of nanomedicine, biomaterial sciences and nanobiotechnology. The physicochemical properties of the surfaces and the nature of their interactions may have an altering effect on the structural stability and activities of biomolecules 30,103,104,106,107 . Computational modelling and simulations can help to unravel the mechanisms of protein surface binding, the determinants of binding specificity as well as thermodynamics adsorption.…”

“…Molecular level information obtained from computational studies has the potential to leverage experimental efforts in drug development. Harnessing the power of theoretical methods such as atomistic MD simulations as well as quantum mechanical (QM) calculations, we elucidated the interactions of A monomer on the surface of a SWCNT as well as provided insights into the effects of surface geometry on the interactions with biomolecules 30,108 . MD simulations have been extensively used to study the binding and interactions of IDPs with surfaces of various biomimetic membrane models as well as membrane permeation phenomenon.…”

“…However, infrequently, thermodynamically equivalent states may be separated by barriers that exceed thermal levels by more than an order of magnitude; such situations may 'trap' specific states, and may trigger the onset of systemic malfunction or disease in biological organisms 26,27 . Specially designed computational studies are often necessary to understand the thermodynamic and kinetic origins of such 'traps' and to strategize plausible physico-chemical means to lower the barriers and repopulate biologically advantageous conformations [28][29][30] . In this article, we attempt to provide an overview of popular computational techniques used for studying IDP conformations, their energy landscapes, kinetics of their transformations and their modulation by the surrounding environment as well as by nanomaterials and small molecules.…”