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

C Harder-Viddal; F Heide; R M Roshko; J Stetefeld

doi:10.1016/j.csbj.2021.06.010

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

Comput Struct Biotechnol J. 2021 Jun 10:19:3531-3541. doi: 10.1016/j.csbj.2021.06.010. eCollection 2021.

Authors

C Harder-Viddal¹, F Heide², R M Roshko³, J Stetefeld^{2

4

5

6}

Affiliations

¹ Department of Chemistry and Physics, Canadian Mennonite University, 500 Shaftesbury Blvd, Winnipeg, Manitoba, Canada.
² Department of Chemistry, University of Manitoba, 144 Dysart Rd, Winnipeg, Manitoba, Canada.
³ Department of Physics and Astronomy, University of Manitoba, 30A Sifton Rd, Winnipeg, Manitoba, Canada.
⁴ Center for Oil and Gas Research and Development (COGRAD), Canada.
⁵ Department of Biochemistry and Medical Genetics, University of Manitoba, Canada.
⁶ Department of Human Anatomy and Cell Science, University of Manitoba, Canada.

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 ${(C}_{2} B_{10} H_{12})$ have been inserted into the four large nonpolar cavities of a nanotube of the right-handed coiled-coil $(R H C C) t e t r a b r a c h i o n$ . 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 $RHCC - t e t r a b r a c h i o n - o r t h o - c a r b o r a n e$ complex 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 $RHCC - n a n o t u b e$ , and the activation barriers for ortho-carborane capture and release support the requirements for rapid cargo uptake coupled with tight binding to the cavities.

Keywords: Boron neutron capture therapy; Double-decoupling; Free energy; Molecular dynamics simulations; Multi-configurational thermodynamic integration; Nonpolar cavities; Ortho-carborane; Right-handed coiled-coil tetrabrachion nanotube; Steered molecular dynamics; Umbrella sampling.