Energetics of Storage and Diffusion of Water and Cyclo-Octasulfur for a Nonpolar Cavity of RHCC Tetrabrachion by Molecular Dynamics Simulations

Abstract

Tetrabrachion forms the key component of the S-layer of Staphylothermus marinus. Molecular dynamics simulations have been used to study the energetics of occupancy of cavity 3 of the right-handed coiled-coil stalk of tetrabrachion by both water molecules and cyclooctasulfur S 8 crowns, as well as to determine possible pathways and free energy barriers for the diffusion of both water and cyclooctasulfur through the peptide walls of RHCC tetrabrachion between cavity 3 and bulk solvent. Calculations of the transfer free energy from solvent to cavity show that clusters of six, seven and eight water molecules are marginally stable in cavity 3, but that occupancy of the cavity by a cyclooctasulfur ring is favoured significantly over water clusters of all sizes. Thermal activation simulations at T = 400 K revealed that water molecules diffusing through the wall pass through a sequence of metastable configurations where they are temporarily immobilized by forming networks of hydrogen bonds with specific wall residues. Calculations of the free energy of these metastable configurations using multi-configurational thermodynamic integration yielded a free energy profile with a principal free energy maximum ∆G ~50 kJ / mol and a slight activation asymmetry in favour of the direction from cavity to solvent. Potential exit pathways for cyclooctasulfur were investigated with the methods of steered molecular dynamics and umbrella sampling. The cyclooctasulfur was steered through a gap in the tetrabrachion wall along a linear path from cavity 3 into the solvent and the resulting trajectory was subdivided into 22 sampling windows. The free energy profile created for the trajectory by umbrella sampling showed a sharp principal maximum as a function of the reaction coordinate with asymmetric free energy barriers ∆G exit ~220 kJ / mol and ∆G entrance ~100 kJ / mol for cavity exit and entrance, respectively.

Boron rich nanotube drug carrier system is suited for boron neutron capture therapy

“…Importantly, these intermediate channels do not seem to disturb the final overall shape and structure of the o- carborane bound nanotube. This same effect has previously been observed for other hydrophobic molecules taken up by RHCC-NT 15 , 16 .…”

Molecular dynamics simulations of ortho-carborane nano-diamond storage within the nonpolar channel cavities of a right-handed coiled-coil tetrabrachion nanotube

“…The ligand movements along the pathways consist of a sequence of rapid hops between transient docking sites where the ligand dwells for relatively long periods of time [45] , a description which matches that of down-channel steering in the current study. Such breathing modes may well play a role not only in the uptake and transport of ortho -carborane by but also in substantiating one of the biological functions proposed for the anaerobic hyperthermophilic archeon S. marinus, namely, the capture and storage of cyclooctasulfur rings from its native sulfur-rich environment in order to make elemental sulfur available as a terminal electron acceptor for energy producing redox-reactions [9] . Future work will focus on searching for evidence of the necessary dynamic structural flexibility in .…”

“…The configuration of cavity waters matched the configuration obtained by X-ray diffraction. Further details may be obtained by consulting reference [9] .…”

“…X-ray diffraction measurements [5] performed on a polypeptide chain fragment of tetrabrachion show that the stalk is a tetrameric right-handed coiled-coil composed of four strands oriented in parallel in a right-handed fashion, forming a nanotube with a central channel and four large non-polar cavities which contain water clusters in the native conformation. The has been shown [5] to be stable at high salt concentrations, temperatures of over 100 ˚C, high pressures and extreme ranges of pH, and several studies have demonstrated that the hydrophobic cavities are able to uptake and store water clusters [5] , elemental sulfur crowns [8] , [9] , atomic metals clusters [10] , and polycyclic hydrocarbons [11] .…”

Modified cyclodextrins solubilize elemental sulfur in water and enable biological sulfane sulfur delivery

“…23 Additional computational investigations have investigated the transit pathways for exchange of water and S 8 within these structures. 24 Further supporting this observation that hydrophobic motifs can increase S 8 solubility, Steudel and Holdt demonstrated that the solubility of S 8 in water can be increased using surfactants, with S 8 concentrations reaching up to 0.1 mM in saturated hexadecyl(trimethyl)ammonium bromide (CTAB) solutions, although reactivity studies were not reported. 25 In addition, the stability of sulfur nanoparticles and sulfur sols, which can be produced both industrially and from sulfur oxidizing bacteria, 26 can also be modulated by different types of surfactants.…”