Structural modification of P-glycoprotein induced by OH radicals: Insights from atomistic simulations.

This study reports on the possible effects of OH radical impact on the transmembrane domain 6 of P-glycoprotein, TM6, which plays a crucial role in drug binding in human cells. For the first time, we employ molecular dynamics (MD) simulations based on the self-consistent charge density functional tight binding (SCC-DFTB) method to elucidate the potential sites of fragmentation and mutation in this domain upon impact of OH radicals, and to obtain fundamental information about the underlying reaction mechanisms. Furthermore, we apply non-reactive MD simulations to investigate the long-term effect of this mutation, with possible implications for drug binding. Our simulations indicate that the interaction of OH radicals with TM6 might lead to the breaking of C-C and C-N peptide bonds, which eventually cause fragmentation of TM6. Moreover, according to our simulations, the OH radicals can yield mutation in the aromatic ring of phenylalanine in TM6, which in turn affects its structure. As TM6 plays an important role in the binding of a range of cytotoxic drugs with P-glycoprotein, any changes in its structure are likely to affect the response of the tumor cell in chemotherapy. This is crucial for cancer therapies based on reactive oxygen species, such as plasma treatment.

Computational modelling of a non-viscous fluid flow in a multi-walled carbon nanotube modelled as a Timoshenko beam.

In the design of nanotube-based fluidic devices, a critical issue is the effect of the induced vibrations in the nanotube arising from the fluid flow, since these vibrations can promote structural instabilities, such as buckling transitions. It is known that the induced resonant frequencies depend on the fluid flow velocity in a significant manner. We have studied, for the first time, the flow of a non-viscous fluid in stubby multi-walled carbon nanotubes, using the Timoshenko classical beam theory to model the nanotubes as a continuum structure. We have obtained the variations of the resonant frequencies with the fluid flow velocity under several experimentally interesting boundary conditions and aspect ratios of the nanotube. The main finding from our work is that, compared to an Euler-Bernoulli classical beam model of a nanotube, the Timoshenko beam predicts the loss of stability at lower fluid flow velocities.