1. Molecular dynamics simulations of ortho-carborane nano-diamond storage within the nonpolar channel cavities of a right-handed coiled-coil tetrabrachion nanotube
- Author
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R. M. Roshko, J. Stetefeld, Fabian Heide, and Candice Harder-Viddal
- Subjects
Steered molecular dynamics ,Nanotube ,Materials science ,Biophysics ,Thermodynamic integration ,Ortho-carborane ,Nonpolar cavities ,Biochemistry ,Right-handed coiled-coil tetrabrachion nanotube ,Multi-configurational thermodynamic integration ,Umbrella sampling ,03 medical and health sciences ,Molecular dynamics ,Boron neutron capture therapy ,0302 clinical medicine ,Tight binding ,Structural Biology ,Genetics ,Molecule ,Double-decoupling ,Free energy ,030304 developmental biology ,0303 health sciences ,Molecular dynamics simulations ,Energy landscape ,Computer Science Applications ,Crystallography ,030220 oncology & carcinogenesis ,Carborane ,TP248.13-248.65 ,Research Article ,Biotechnology - Abstract
Graphical abstract Molecular dynamics simulations have been performed on a complex in which clusters of boron in the form of molecules of the nanodiamond ortho-carborane (C2B10H12) have been inserted into the four large nonpolar cavities of a nanotube of the right-handed coiled-coil RHCC. The techniques of multi-configurational thermodynamic integration, steered molecular dynamics and umbrella sampling have been combined to investigate the energetics of storage of ortho-carborane in the cavities and to map out the free energy landscape of the RHCC-tetrabrachion-ortho-carboranecomplex along the central channel and along directions transverse to the central channel. The purpose of the study was to explore potential pathways for the diffusion of ortho-carborane between the cavities and the solvent and to assess the stability of the complex as a possible drug delivery system for boron neutron capture therapy (BNCT). The investigation reveals a complex free energy landscape with a multitude of peaks and valleys, all of which can be related to specific architectural elements of the RHCC-nanotube, and the activation barriers for ortho-carborane capture and release support the requirements for rapid cargo uptake coupled with tight binding to the cavities., Molecular dynamics simulations have been performed on a complex in which clusters of boron in the form of molecules of the nanodiamond ortho-carborane (C2B10H12) have been inserted into the four large nonpolar cavities of a nanotube of the right-handed coiled-coil (RHCC)tetrabrachion. The techniques of multi-configurational thermodynamic integration, steered molecular dynamics and umbrella sampling have been combined to investigate the energetics of storage of ortho-carborane in the cavities and to map out the free energy landscape of the RHCC-tetrabrachion-ortho-carboranecomplex along the central channel and along directions transverse to the central channel. The purpose of the study was to explore potential pathways for the diffusion of ortho-carborane between the cavities and the solvent and to assess the stability of the complex as a possible drug delivery system for boron neutron capture therapy (BNCT). The investigation reveals a complex free energy landscape with a multitude of peaks and valleys, all of which can be related to specific architectural elements of the RHCC-nanotube, and the activation barriers for ortho-carborane capture and release support the requirements for rapid cargo uptake coupled with tight binding to the cavities.
- Published
- 2021